Pancreatic Endocrine Dysfunction Is Associated with Growth Failure in HIV Positive Children

The pancreatic endocrine system normally guarantees a quick and efficient response to daily metabolic perturbations, but associated data for HIV patients are lacking. A prospective study was performed to evaluate pancreatic endocrine secretion and its possible association with failure to thrive among HIV-infected children.

Fourteen well-nourished, prepubertal, HIV-infected children (6 boys and 8 girls; age range, 5-11 years), none of whom were receiving protease inhibitors, and 16 clinically healthy sex- and age-matched children formed the patient group and the control group, respectively.

At yearly follow-up examinations, insulin, glucagon, C-peptide, and glucose levels were measured; the ratio of insulin to glucose, the ratio of insulin to glucagon, and the homeostasis model assessment (HOMA) index were calculated; the glucagon test was administered; and growth hormone, thyroid-stimulating hormone, adrenocorticotropic hormone, cortisol, and lipid patterns were evaluated.

Results

Insulin, glucagon, C-peptide, glucose, and HOMA measurements were significantly higher among patients, compared with control subjects, at all 3 follow-ups performed to date.

The glucagon test revealed a normal glycemic response in all the healthy control subjects and a significantly impaired response in 11 patients.

A significant correlation emerged between the ratio of insulin to glucagon and the growth velocity of HIV-infected children.

Conclusion.    

The authors conclude, “To our knowledge, the present study provides the first evidence of altered pancreatic endocrine secretion and its association with growth failure among HIV-infected children.”

Discussion

Endocrine dysfunction has been extensively reported in HIV-infected adults and children; however, at present, data documenting pancreatic function in HIV-infected children are lacking.

 Furthermore, there are few available data on beta-cell dysfunction in adult HIV-infected patients receiving treatment with protease inhibitors. In effect, highly active antiretroviral therapy determined severe metabolic disturbances-namely, insulin resistance.

The etiology of this syndrome appears to be multifactorial; in addition to antiviral drugs, hypercytokinemia and HIV infection itself, including the virally encoded molecules Vpr and Tat (virion-associated accessory proteins), could contribute to the development of insulin resistance.

Against this background, the results of the prospective study reported here constitute, to our knowledge, the first evidence of altered pancreatic endocrine secretion and its association with growth failure, which is one of the most sensitive indicators of disease progression and has been extensively reported to occur in HIV-infected children.

In fact, to our knowledge, the results of the present study demonstrate, for the first time, that insulin, glucagon, and C-peptide levels and insulin resistance (as evaluated by HOMA) are markedly greater among HIV-infected children than among sex- and age-matched healthy control subjects.

Moreover, a close association was found between altered pancreatic endocrine secretion and failure to thrive. In particular, an association was observed between the ratio of insulin to glucagon and growth velocity at all 3 evaluations.

Simple biochemical parameters, such as glucagon and insulin levels, could be routinely measured in consecutive clinical assessments, to document metabolic alterations that, although apparently are only secondary, may, in fact, be very important in the regulation of growth among HIV-infected children.

Additional studies are needed of larger samples of HIV-seropositive children, including children who are evaluated after receiving combination therapies, to better define the role of endocrine pancreas dysfunction in the development of a growth mechanism alteration and to clarify whether therapies involving protease inhibitors are able to influence this derangement of the endocrine pancreas.

Finally, the long-term consequences of these endocrine pancreatic changes and the possible influence of beta-cell dysfunction on lipodystrophy in individuals receiving combination therapy require investigation both in adults and children.

Departments of  Internal Medicine and Medical Therapy and Paediatrics, IRCCS C. Mondino Foundation, and Institute of Infectious Diseases, University of Pavia, Pavia, Italy.

08/18/04

Reference
M Randanelli and others. Endocrine Pancreatic Dysfunction in HIV-Infected Children: Association with Growth Alterations. The Journal of Infectious Diseases 190(5): 908-912. September 1, 2004.