Administration of human umbilical cord blood to low birth weight infants may prevent the subsequent development of type 2 diabetes

https://doi.org/10.1016/j.mehy.2005.12.024Get rights and content

Summary

Both epidemiological and experimental studies have shown that impaired growth in utero due to maternal malnutrition, resulting in low birth weight, is associated with a high incidence of glucose intolerance, insulin resistance, and type 2 diabetes in adult life. Maternal malnutrition is a worldwide problem and unavoidable; therefore, prevention of type 2 diabetes in low birth weight infants who reach adulthood is difficult to achieve. Administration of human umbilical cord blood (HUCB) mononuclear cells into type 1 and type 2 diabetic mice has been shown to improve both their blood glucose levels and survival. It has also been shown that the progenitor cells derived from HUCB improve not only glycemia but also other disease conditions, including systemic lupus erythematosis, amyotrophic lateral sclerosis, Alzheimer’s disease, stroke, brain damage in animals and certain malignancies in humans. Transfusion of unrelated HUCB, although abundantly available, is underutilized as a therapeutic agent. Therefore, we propose the hypothesis that transfusion of HUCB to low birth weight infants be considered a therapeutic modality to prevent the development of type 2 diabetes in their adulthood.

Introduction

A number of epidemiological and experimental studies have shown that impaired intrauterine growth, resulting in low birth weight (less than the 10th percentile), is associated with a variety of adult-onset diseases, including type 2 diabetes, hypertension, hyperlipidemia, cardiovascular disease, stroke [1], [2], [3], [4], [5], [6], [7], [8], [9], [10] and kidney disease [11], [12]. The common underlying mechanism for most of these disease conditions seems to be glucose intolerance and insulin resistance with hyperinsulinemia. Worldwide, maternal malnutrition, leading to poor fetal nutrition, seems to be the important cause of fetal growth retardation [8]. In this under-nourished fetus, it is hypothesized that the nutrient supply to the brain is well preserved at the expense of the other organs. For example, the growth of the pancreas and kidney and possibly the skeletal muscle is reduced. Rats fed a low protein diet during pregnancy results in significant reduction in pancreatic β-cell proliferation and islet cell size in the neonates [13]. In addition, apoptosis of β-cells and decreased islet vascularization was observed in 14-day-old neonates born to low protein diet mothers [14]. Thus, the reduction in β-cell mass occurs at the expense of the growth of the brain. The net result of this “trade off” is a decrease in insulin secretion in the low birth weight infant. Decreased insulin secretion alone is not sufficient to cause glucose intolerance, because the under-nourished infant is usually thin and may have normal insulin sensitivity. However, overfeeding during childhood with development of obesity in adulthood may cause glucose intolerance and insulin resistance, leading to type 2 diabetes later in life [7], [8].

Section snippets

Hypothesis

Lifestyle modification with diet and appropriate caloric intake to improve insulin secretion in the offspring of malnourished pregnant mothers will help prevent the development of type 2 diabetes later in life. However, such a strict lifestyle modification in a growing child is not always feasible. Cherif et al. [15] supplemented pregnant rats on low protein diet with taurine, which stimulates the release of insulin from islet cells, and found restoration of insulin release from malnourished

References (53)

  • E.J. Boyko

    Proportion of type 2 diabetes cases resulting from impaired fetal growth

    Diabetes Care

    (2000)
  • A.A. Jackson

    Nutrients, growth, and the development of programmed metabolic function

    Adv Exp Med Biol

    (2000)
  • M.H. Vickers et al.

    Fetal origins of hyperphagia, obesity, hypertension and postnatal amplification by hypercaloric nutrition

    Am J Physiol Endocrinol Metab

    (2000)
  • C.N. Hales et al.

    The thrifty phenotype hypothesis

    Br Med Bull

    (2001)
  • P.L. Hofman et al.

    Premature birth and later insulin resistance

    N Engl J Med

    (2004)
  • M.A. Sperling

    Prematurity—a window of opportunity?

    N Engl J Med

    (2004)
  • B.M. Brenner et al.

    Glomeruli and blood pressure. Less of one, and more of the other?

    Am J Hypertens

    (1988)
  • P. Rossing et al.

    Low birth weight. A risk factor for development of diabetic nephropathy?

    Diabetes

    (1995)
  • A. Snoeck et al.

    Effect of a low protein diet during pregnancy on the fetal rat endocrine pancrease

    Biol Neonate

    (1990)
  • J. Petrik et al.

    A low protein diet alters the balance of islet cell replication and apoptosis in the fetal and neonatal rat and is associated with a reduced pancreatic expression of insulin-like growth factor-II

    Endocrinology

    (1999)
  • H. Cherif et al.

    Effects of taurine on the insulin secretion of rat fetal islets from dams fed a low-protein diet

    J Endocrinol

    (1998)
  • V.K. Ramiya et al.

    Reversal of insulin-dependent diabetes using islets generated in vitro from pancreatic stem cells

    Nature Med

    (2000)
  • B. Soria et al.

    Insulin-secreting cells derived from embryonic stem cells normalize glycemia in streptozotocin-induced diabetic mice

    Diabetes

    (2000)
  • S. Assady et al.

    Insulin production by human embryonic stem cells

    Diabetes

    (2001)
  • N. Lumelsky et al.

    Differentiation of embryonic stem cells to insulin-secreting structures similar to pancreatic islets

    Science

    (2001)
  • S. Ryu et al.

    Reversal of established autoimmune diabetes by restoration of endogenous β cell function

    J Clin Invest

    (2001)
  • Cited by (0)

    View full text