Lipodystrophy and metabolic changes in children

Little attention has been given to studies of changes in regional fat and lipid metabolism in children although there have been several case reports and surveys that indicate that they also experience these symptoms.

After the age of five, indices of central fat in children are relatively normal and changes in the subscapular : triceps subcutaneous fat ratio only changes again at the age of 16. Also, insulin sensitivity and triglyceride levels are asociated with measures of central fat in children and in adolescents. There haven’t been studies looking at changes in regional fat and lipid metabolism in HIV-infected children.

In one of the most practical and clinically relevant oral presentations, Dr Stephan Arpadi from StLukes-Roosevelt, New York looked at whether fat redistribution and triglyeride (TG) and cholesterol (CHL) changes could be detected in an observational clinical cohort of 28 pre-pubescent children. DEXA, random triglyceride and cholesterol levels, PRC RNA-viral load and lymphocyte subset were analysed at baseline and follow-up between and within groups using OR and Fisher exact test for associations. Fat redistribution (FR) was defined as requiring both a decrease in peripheral fat (arm and leg) and an increase in trunk fat and TG and CHL were compared to expected normal values from the US National Child Evaluation Programme.

The mean age was 7.5 (±2.3, range 4-12) with a normal weight for age but low height for age z-scores. Other mean baseline characteristics of the group ± SD included BMI (kg/m2) – 16.7±3.2; Total body fat – 20.4±8.3; CD4 count 457 ±397; CD4% 19.8 ±12.4; Log HIV RNA 4.12 ± 0.74.

Although only one of these children had been associated with a prior lipodystrophy concern, 8 (29%) were identified as having fat redistribution with both fat accumulation and loss, 3 children had only fat loss and half the children had weight gain only.

Changes in weight and body composition in children with and without fat redistribution (FR) were as follows:

The only baseline factors for these two groups that were significantly determinant were baseline viral load and CD4 count (p<0.05) and CD4% (p<0.01). Age, sex, race, BMI, body fat and trunk extremity ratios were not found to be significant. PI-use (mainly saquinavir and ritonavir) and d4T-use were also found to correlate although no allowance was made for previous NRTI use and the FR group were generally more heavily treated. Baseline TG and CHL were not significant at follow up, but in the fat redistribution group in the paired analysis these did became apparent. Factors associated with >130mg% TG were fat redistribution (OR 11.4, 95%CI 1.0-13.5, p=0.058) and PI use (OR 3.0, 95%CI 1.7-5.3, p=0.02).

The study concluded that features associated with fat redistribution and TG alterations are occurring in children, although at the moment they seem to be less severe than in adults. Also, that indices of visceral adiposity may be more sensitive markers for these changes than total fat. Although this was only a small study, children currently are faced with the prospect of lifelong treatment and monitoring all children within a national cohort would seem to offer many benefits – especially given the questions of whether this poses a higher risk for atheosclerosis and cardiovascular factors.

Arpadi, S – Changes in Regional Body Fat and Serum Triglycerides and Cholesterol in HIV-infected Children. Abstract O21. 2nd Intl Workshop on Adverse Drug Interactions and Lipodystrophy, Toronto, Sep 2000.

	Univariate OR p		Multivariate OR p
Weight pre-ARV	0.95	0.013	0.94	0.006
Lactate	1.98	0.004	2.39	0.002