Pathophysiology
P-I-5. Obesity–Diabetes, Case 1
肥満・糖尿病 症例1
A 48-year-old obese female patient feels her left leg is weaker - sometimes both feet numb. It started 3 weeks ago. Three years ago on a free screening she had 7.8 mmol/l random blood sugar and a 5.8 mmol/l cholesterol level. Since she had no complaints, she did not continue/follow up the examination. She complains about frequent urination at night, but no blood in the urine, and no burning sensation or pain is present.
Physical examination: dry and broken skin of the feet. She feels light tingling on both lower extremities.
- Blood pressure: 165/100 Hgmm
- Height: 159 cm
- Weight: 92 kg
Laboratory results (fasting):
- Na⁺: 139 mmol/l
- K⁺: 4 mmol/l
- Cl⁻: 102 mmol/l
- HCO₃⁻: 22 mmol/l
- BUN: 5 mmol/l
- Creatinine: 79 mmol/l
- Glucose: 12.3 mmol/l
- ASAT: 19 U/L
- ALAT: 13 U/L
- ALP: 43 U/L
- gGT: 115 U/L
- Uric acid: 458 μmol/L
- T. bilirubin: 18 μmol/L
- D. bilirubin: 2.8 μmol/l
- Total cholesterol: 6.37 mmol/l
- HDL: 0.7 mmol/l
- Triglycerides: 5.18 mmol/l
- HbA1c: 9.2%
Urinalysis:
- pH: 5.8
- Specific gravity: 1008 g/L
- Bilirubin: neg.
- Protein: neg.
- Ketone test: neg.
- Sugar: pos.
- No red blood cells, white blood cells, or bacteria in urine sediment.
Key Quotes & What They Tell Us
| Quote / Value | Interpretation |
|---|---|
| HbA1c 9.2%; fasting glucose 12.3 mmol/L; urine sugar positive | Poorly controlled diabetes mellitus — HbA1c reflects chronic hyperglycaemia, glucosuria confirms threshold exceeded |
| “frequent urination at night” | Polyuria from osmotic diuresis driven by glucosuria |
| “left leg … weaker … both feet numb”; “light tingling”; “dry and broken skin of the feet” | Diabetic peripheral sensorimotor neuropathy with autonomic skin changes |
| Weight 92 kg, height 159 cm (BMI ≈ 36.4); BP 165/100 mmHg | Obesity and hypertension |
| Total cholesterol 6.37, HDL 0.7 (low), triglycerides 5.18 (high) | Atherogenic dyslipidaemia |
| gGT 115 U/L (high); uric acid 458 µmol/L (high) | Likely non-alcoholic fatty liver and hyperuricaemia — further metabolic-syndrome features |
| Ketone test negative; HCO₃⁻ 22 mmol/L (normal) | No ketoacidosis — consistent with type 2 rather than type 1 diabetes |
Key Points
- Diagnosis: Type 2 diabetes mellitus, poorly controlled (HbA1c 9.2%), recognised only after years of neglected screening abnormalities.
- Complication already present: Diabetic peripheral neuropathy.
- Metabolic syndrome: Central obesity, hypertension, atherogenic dyslipidaemia, hyperuricaemia, and fatty liver coexist.
- Pathophysiology: Insulin resistance → chronic hyperglycaemia → osmotic diuresis and microvascular nerve damage.
- Distinction: Negative ketones and normal bicarbonate separate this from type 1 diabetes / DKA.
一問一答
▶What is the diagnosis in an obese patient with HbA1c 9.2%, fasting glucose 12.3 mmol/L, and glucosuria but no ketones?
Poorly controlled type 2 diabetes mellitus.
▶What does HbA1c reflect, and what does 9.2% indicate?
It reflects chronic (~3-month) average glycaemia; 9.2% indicates poorly controlled hyperglycaemia.
▶What do leg weakness, foot numbness, tingling, and dry/broken foot skin indicate in this diabetic patient?
Diabetic peripheral sensorimotor neuropathy with autonomic skin changes.
▶Why does urine sugar become positive in diabetes?
When blood glucose exceeds the renal threshold, glucose is no longer fully reabsorbed and spills into the urine.
▶Why does this patient have nocturnal polyuria?
Glucosuria causes an osmotic diuresis, increasing urine output.
▶What is the underlying pathophysiology of type 2 diabetes complications in this patient?
Insulin resistance → chronic hyperglycaemia → osmotic diuresis and microvascular nerve damage.
▶What distinguishes this case from type 1 diabetes / DKA?
Negative ketones and normal bicarbonate (22 mmol/L) exclude ketoacidosis, consistent with type 2 diabetes.
▶What features in this patient indicate metabolic syndrome?
Central obesity (BMI ~36), hypertension, atherogenic dyslipidaemia, hyperuricaemia, and fatty liver.
▶What lipid pattern defines the atherogenic dyslipidaemia here?
High total cholesterol (6.37), low HDL (0.7), and high triglycerides (5.18 mmol/L).
▶What do high gGT and high uric acid suggest in this patient?
Likely non-alcoholic fatty liver disease and hyperuricaemia — further metabolic-syndrome features.
▶Why was the diabetes diagnosed late despite earlier abnormal screening?
She had no symptoms and did not follow up the earlier elevated glucose/cholesterol, so it went untreated for years.
▶Why is a complication (neuropathy) already present at diagnosis of type 2 diabetes?
Type 2 diabetes is often silent for years, allowing chronic hyperglycaemia to damage nerves before diagnosis.
▶Why is insulin resistance central to type 2 diabetes?
Tissues respond poorly to insulin, so glucose uptake falls and the liver overproduces glucose, causing hyperglycaemia.
▶Why does the dry, broken foot skin reflect autonomic neuropathy?
Autonomic damage reduces sweating, leaving skin dry and cracked — a risk factor for diabetic foot ulcers.
▶Why does the absence of urinary RBCs, WBCs, and bacteria matter here?
It excludes a urinary tract infection as the cause of her nocturnal urinary symptoms, pointing to osmotic diuresis.
▶How does obesity contribute to type 2 diabetes?
Excess adipose tissue promotes insulin resistance and chronic low-grade inflammation, worsening glucose control.
▶Why is low specific gravity (1008) seen despite high glucose in this case?
Large dilute urine volumes from osmotic diuresis can keep specific gravity low.
▶Why does chronic hyperglycaemia damage peripheral nerves?
It drives ROS formation, AGE accumulation, and microvascular ischaemia that injure nerve fibers.
▶Why is regular screening and follow-up important after an abnormal glucose result?
Early detection and treatment can prevent or delay irreversible complications like neuropathy.
▶Why does normal bicarbonate with negative ketones rule out DKA in this patient?
DKA requires ketone overproduction and a metabolic acidosis (low HCO₃⁻); both are absent here.