Hypertriglyceridemia associated with eruptive xanthomas and lipemia retinalis in newly diagnosed D.M

2. Case Summary
Five years old girl………
• previously healthy presented with a 4-day
history of progressive epigastric abdominal
pain, polydepsia, secondary nocturnal
enuresis and history of weight loss.
• No fever ?
• Past History : IDA …..
• F.H & D.H: nothing significant

3. Her initial assessment revealed tachypnea with
Kussmaul's respiration, tachycardia and
moderate dehydration.
CNS; Lethrgic, revealed generalized body
weakness
chest; harsh vesicular breathing with good air
entry.
Heart: Audible S1 & S2with systolic murmur in
the apex.
Abdomen: liver and spleen just palpable.
Case Summary
On Examination

4. o The girl was hyperglycemic (plasma glucose
level more than 600 mgdl) and acidotic (pH
7.14, bicarbonate level 3.9 mmol/L), with
urinalysis revealing ketonuria and glucosuria.
o CBC & ESR, RFTs, LFTs: within normal limits.
Case Summary Investigations

5. Diagnosis…..

6. Treatment
o After admission,
o appropriate fluid resuscitation and
o insulin treatment were started.
o The patient's diabetic ketoacidosis resolved over 24
hours,
o at which point a diabetic diet was introduced along
with
o subcutaneous insulin therapy (lantus and Novorapid
basal bolus regime).

7. • On further enquiry… Skin lesions were
observed; non-tender yellow papules with
creamy-colored centers on face & extensor
surfaces of the arms, hands and feet.
Case Summary

8. • Ophthalmoscopic examination showed
creamy white retinal vessels with a faded
pinkish white retinal back ground both in the
periphery and posterior pole of the retina.
Case Summary

9. • Laboratory findings showed a grossly lipemic
serum with elevated serum levels of
triglycerides 2869 mg/dl, cholesterol
498mg/dl, Amylase 45 and HbA1c was 14.8%.
Case Summary

10. Diagnosis…..

11. Treatment
• Given the extent of her hyperlipidaemia and
hypergltcemia, the patient put on follow up;
• the patient continued on a diabetic diet along
with subcutaneous insulin therapy, and ..
• after one month all her investigations were
repeated; serum glucose and lipid profile were
normal, and ….
• Now the patient has no any skin lesions (eruptive
xanthomas) clinically nor lipemia retinalis on
Ophthalmoscopic examination.

12. Before treatment After medical treatment
Conclusion:
This case illustrates a young person with Hypertriglyceridemia associated with
eruptive xanthomas and lipemia retinalis in newly diagnosed diabetes mellitus.

13. Some theory …..

14. Brief review of lipoprotein metabolism
• Lipoproteins, which transport non-water soluble
cholesterol and triglycerides in plasma.
• Lipoproteins are generally classified according to
their density as:
• Chylomicron,
• Very Low Density Lipoprotein (VLDL),
• Intermediate Density Lipoprotein(IDL),
• Low Density Lipoprotein (LDL) and
• High Density Lipoprotein (HDL).

15. o Chylomicrons:
o The formation of chylomicrons takes place in the enterocytes.
• Chylomicrons are secreted into the lymphatic circulation before
entering the bloodstream.
o In plasma, chylomicrons by the lipoprotein lipase form smaller,
triglyceride-poorer particles known as chylomicron-remnants.

16. • Chylomicron-remnants are cleared by the
liver through:
• LDL B/E receptor or
• LRP receptor (LDL-receptor related protein).

17. • VLDL particles are secreted by the liver.
• In plasma, triglycerides of VLDLs are
hydrolyzed by the lipoprotein lipase leads to
the formation of IDL particles.

18. • IDL particles are either:
• cleared by the liver through LDL B/E receptor
or
• further metabolized by hepatic lipase to form
LDLs.

19. • LDL is the final product.
• LDL is the main cholesterol-bearing
lipoprotein in plasma.
• Clearance of LDL is mediated by the LDL B/E
receptor.
30%
70%

20. • HDLs particles are secreted by the hepatocytes .
• Within HDL particles, free cholesterol is esterified by LCAT
(Lecithin Cholesterol AcylTransferase) leading to the
formation of HDL3 particles.
• The fusion of 2 HDL3 particles leads to the formation of one
larger size HDL2 particle.
• HDL2 lipoproteins are degraded by the hepatic lipase and
the endothelial lipase, leading to the formation of HDL
remnant particles that are cleared by the liver.
30%
70%

21. Insulin and lipoprotein metabolism
• Insulin plays a central role in the regulation of
lipid metabolism.

22. 1: insulin inhibits hormone-sensitive lipase.
2 : insulin activates LipoProtein Lipase (LPL)
3: insulin inhibits hepatic VLDL production.
4: insulin increases LDL B/E receptor expression.
5:insulin activates LCAT (Lecithin Cholesterol AcylTransferase)
6: insulin activates Hepatic Lipase (HL).

23. Conclusion
• This case illustrates a young person with
Hypertriglyceridemia associated with eruptive
xanthomas and lipemia retinalis in newly
diagnosed diabetes mellitus.
• Previous proposals to explain this phenomenon
include: genetic abnormalities of lipoprotein
lipase 1 , or a transient decrease in lipoprotein
lipase activity secondary to insulin deficiency 2,3 .
1 - Karagianni C, StabouliS, Roumeliotou K, et al. Severe hypertriglyceridaemiain diabetic ketoacidosis: clinical and genetic study. Diabet
Med 2004;21:380–2.
2 - Nyamugunduru G, Roper H. A difficult case: Childhood onset insulin dependent diabetes presenting with severe hyperlipidaemia. BMJ.
Jan 4, 1997; 314(7073): 62–65.
3 - Abbate S, Brunzell J. Pathophysiology of hyperlipidemia in diabetes mellitus. Cardiovasc Pharmacol. 1990;16 Suppl 9:S1-7.

24. THANKS FOR YOUR ATTENTION