Laboratory evaluation of carbohydrate metabolism

Question 1

1. Is it possible that someone:
   
   • a) has glucosuria at a serum glucose concentration of 5 mmol/l?
   • b) does not have glucosuria at a serum glucose concentration of 15 mmol/l?

(+treatment)

Answer 1

• a) Yes, if there is an issue with glucose reabsorption in the proximal convoluted tubule, known as “renal glucosuria”**. This can be seen in **“Fanconi syndrome”, a disorder with multiple possible congenital or acquired causes leading to impaired reabsorption of various molecules from the kidney.
• b) Yes, if there is a problem with glomerular filtration, such as decreased GFR via renal artery obstruction or diabetic nephropathy.
  
  • normal GFR = 120-130 ml/min
  • end-stage diabetic kidney = 5-10 ml/min
  • tubular glucose reabsorption threshold @ normal GFR = 10 mmol/l , but at a low GFR, reabsorption of a higher concentration of glucose can be performed
  • pt with severely ↓ GFR should be put on dialysis and kidney transplant list

Question 2

2. A 15-year-old girl has been losing weight in spite of having a good appetite , and she feels tired lately. She has been admitted to a hospital for vomiting , being dizzy and disoriented.

• Laboratory findings:
  
  • urine glucose: strongly positive
  • ketone bodies: positive
  • blood glucose: 28.5 mmol/l
  • blood pH: 7.1
  • serum K+: 5.4 mmol/l

What is your diagnosis, and what is to be done with her?

Answer 2

• Current condition: Diabetic ketoacidosis , as indicated by the blood + urine glucose (diabetic), ketone bodies (keto-) and low PH/high K + (-acidosis!).
• Underlying cause: Type 1 Diabetes Mellitus , as indicated by the patient’s age, weight loss (rather than gain seen in type 2), and blood/urine glucose (> 11 mM random blood glucose indicates DM without need for further testing). Type 1 can be confirmed by checking for islet cell/insulin/glutamic acid decarboxylase autoantibodies
  .————————————————————————-
• Symptom explanations:
  
  • tiredness due to “fasting” cells (no insulin to stimulate glucose uptake)
  • weight loss due t_o use of muscle protein & TAG (glycerol) from adipose tissue_ for gluconeogenesis
  • dizziness/disorientation via dehydration (glucose → osmotic diuresis)
  • nausea via acidosis → vomiting helps excrete acid
• Hyperkalemia occurs because: ↓ glucose in cells → ↓ Na/K-ATPase activity → ↑ EC K + and metabolic acidosis → renal H + excretion → renal K + reabsorption
  .————————————————————————-
• Treatment: IV fluids and insulin (2-3 units/hr), both slowly to avoid complications
  
  • GLUT2/3 transport in neurons can become dysfunctional with fast ↓ glucose so a 5 mM/day reduction is best
  • cerebral edema can occur with fast ↑ fluids
  • pH monitoring and K+ monitoring is important, as there may be a hypokalemic rebound when Na/K-ATPases begin to function again, requiring K + infusion
  • older T1DM patient may require bicarbonate for pH normalization

Question 3

3. A 56 year-old man who used to be healthy complains of polyuria.

• Laboratory findings:
  
  • fasting blood glucose: 7.3 mmol/l,
  • fasting blood glucose a week later: 7.6 mmol/l.

What is your diagnosis, and what would you do with him?

Answer 3

• Diabetes mellitus , a fasting blood glucose > 7 mmol/l confirms this. Can check autoantibodies to confirm which type
  (presence of Abs would suggest LADA ),

but it is likely type 2 because of his age and the not-so-high glucose level.

• Can be treated with diet , exercise and oral antihyperglycemics (sulfonylureas, etc.)
• Should also check for retinopathy , peripheral neuropathy , other risk factors for atherosclerosis (smoking, htx), and nephropathy (proteinuria, etc.)

Question 4

4. A 60 year-old woman, weighing 90 kg. Fasting blood glucose concentration: 6.9 mmol/l. Neither

glucose nor ketone bodies are found in her urine.

• The results of oral glucose tolerance test:
  
  • fasting value: 6.4 mmol/l
  • 2h value: 8.5 mmol/l

What is your diagnosis, and what would you advise to her?

Answer 4

• Impaired Glucose Tolerance (IGT) -

because of her 2-hr OGTT value >7.8 but <11 .

• 20-25% of IGT/IFG patients later develop T2DM
• Patient should lose weight if obese (90 kg is high unless she’s tall), reduce dietary carbohydrates, exercise and have her blood glucose checked regularly .

Question 5

5. Laboratory findings of a person:

• fasting blood glucose: 6.2 mmol/l
• Oral glucose tolerance test was performed on another occasion:
  
  • fasting value: 6.3 mmol/l
  • 2h value: 6.5 mmol/l.

What is the diagnosis, and what is the clinical significance of it?

Answer 5

• Impaired Fasting Glucose (IFG) - just indicates higher risk of developing T2DM

Question 6

6. What are your options to check the glucose metabolism of your diabetic patient, to decide if the current treatment needs to be changed or not?

Answer 6

• Home glucose test kit - a “strip” method, not as accurate as a lab, but a record kept of these values is useful.
• Fasting blood glucose + HbA1c taken at the clinic every 3 months with a target HbA1c of 6-7%
• Yearly check-ups for the various diabetic complications … neuro-, nephro-, retinopathy
• (another glycosylated serum protein “ fructosamine ” can be checked but only indicates avg. glucose levels of past 2 weeks)

Question 7

7. A diabetic patient treated with insulin has a fasting blood glucose concentration of 6.4 mmol/l. No glucose (I assume they mean urinary) was detected on the morning of the examination.

The Hb-A1C level is 10 % (normal value: 3–6 %).

Do you think the control of glucose concentration was acceptable in the last 1–2 months?

Answer 7

No, because the target HbA1c is 6-7% for treated diabetics. Either the patient is not following a proper diet or the treatment needs to be adjusted. (The fasting value btwn 6-7 mM also would indicate a need for

OGTT if the patient had not already been diagnosed as DM.)

Question 8

8. A type 1 diabetic man has been eating very little for the last couple of days, due to a febrile illness, so he decided to stop administering his insulin. He checked his blood glucose, because he felt worse and worse, and was surprised to see, that it was more than 20 mM.

What is the explanation?

Answer 8

A type 1 DM patient who stops insulin administration will have intense gluconeogenesis due to extremely low endogenous insulin production. Febrile illness will also have gluconeogenic effects via increased cortisol + cytokines seen in acute infections.

Question 9

9. A diabetic man treated with insulin skipped his late evening meal before going to bed,without any change in his insulin administration. He has been sweating a lot during the night, and glucose has been detected in his urine in the morning.

What is the explanation for this?

Answer 9

• Paradox/Somogyi Effect - no meal + insulin = hypoglycemia → sympathetic activation → sweating + ↑ insulin antagonist hormones (cortisol/glucagon/GH/catecholamines/T3/T4) → gluconeogenesis → hyperglycemia + morning glucosuria
• treatment is actually carb intake and/or less insulin administration
• (not sure about that part… that’s what Tunde said… i guess carbs → ↓ insulin antagonists/gluconeogenesis and then ↓ blood sugar? but seems weird … also Wikipedia says the Somogyi effect might be fake…)

Question 10

10. A man with type 1 diabetes, cooperating very well with his physician, keeps his diet and insulin administration very precisely. He is an employee of a bank, and currently attends a team building training, a several-day-long survival tour causing significant physical exertion. The man, who is known to be reserved, starts shouting and quarreling with his coworkers, then he begins to sweat, quiver and develops cramps.

What do you think is the explanation of his behaviour?

Answer 10

• Hypoglycemia due to the physical exertion without either lowering insulin or i_ncreasing carb intake.(?)_
  
  • Exercise → ↑ GLUT4 translocation → ↑ glucose uptake in muscle → ↓ blood glucose
• Low blood sugar → sympathetic activation → sweating
• Direct hypoglycemic CNS effects → mood alteration

Question 11

11. A woman was admitted to the hospital with the complaint of recurrent seizures. Her fasting blood glucose level is 2.7 mmol/l.

What can cause these symptoms? What tests would you perform to establish the diagnosis?

Answer 11

• if diabetic - over-administration of insulin
• if not diabetic - insulinoma / alcohol (via ↓ NAD + → ↓ gluconeogenesis)/ fever / sepsis / Addison’s / hypothyroidism
• Tests:
  
  • imaging - for insulinoma, 80% in pancreas, 20% in GI tract
  • C-peptide - will be ↓ in insulin overdose, or high in insulinoma
  • ACTH stimulation test - to check for Addison’s

Question 12

12. A breast-fed infant was admitted to the hospital with weight loss, vomiting and jaundice.

Blood glucose level is somewhat low. Glucose is not, but a reducing substance is detectable in the urine.

What is the likely diagnosis?

Answer 12

• Galactosemia - a deficiency of galactose-1-phosphate uridylyltransferase enzyme.
• Inability to convert galactose to glucose → weight loss
• Fermentation of galactose in gut → vomiting, distension, pain
• Galactose metabolite galactitol builds up in liver + spleen → hepatosplenomegaly + jaundice
• The “reducing substance” in the urine is galactose.
• Can be treated by excluding dietary galactose (milk).

Question 13

13. A small boy gets regularly sick after eating sugar containing foods: he is sweating, feels dizzy, vomits. He does not eat sweets for this reason. These symptoms were shown to be caused by reactive hypoglycemia, on examination.

What is the likely diagnosis?

Answer 13

• Fructose intolerance - lack of aldolase B enzyme (fructose-1-P → glyceraldehyde + dihydroxyacetone-P)
• leads to “phosphate trapping” via accumulation of F-1-P and inhibited glucose/ATP production