Impaired carbohydrate metabolism:
Impaired glucose tolerance and diabetes
mellitus may be the consequence of β-cell destruction secondary to iron
overload, chronic liver disease, viral infection and/or genetic factor. The
pathogenesis resembles type-2 diabetes, with the difference in the age of onset
(it may start in the second decade of life) and slow progression of
disturbances in glucose metabolism and insulin secretion. Diabetes in
thalassemia is rarely complicated by ketoacidosis (De Sanctis, 1998).
Chronic hepatitis C may play a role in the development
of abnormal glucose tolerance. An association between diabetes and genotyping
IVS II nt 745 was found. Patients with this particular genotype are advised to
check their blood glucose every 6 months to detect early occurrence of diabetes
(Khalifa et al., 2004).
The reported incidence of impaired glucose tolerance in
thalassemia major is 4-24% and that of diabetes mellitus is 0-26% (Khalifa
et al., 2004). Although insulin deficiency secondary to pancreatic
islet iron deposition has been assumed to be the principle cause, reports of
hyper-insulinema with abnormal glucose tolerance testing may suggest a role of
insulin resistance. Moreover an increase in insulin resistance has been
reported in thalassemics even without overt impaired glucose tolerance or
diabetes, suggesting the advent of insulin resistance before the onset of
glucose intolerance or diabetes (Cario et al., 2003). The insulin
resistance has been postulated to be at the level of the liver (due to iron
deposition), where it may interfere with the insulin’s ability to suppress
hepatic glucose uptake, and also at the level of the muscle, where iron
deposits may decrease the glucose uptake (Chern et al., 2001).
The increase in insulin levels has been postulated due to reduced hepatic
insulin extraction rather than an increase in the secretory response (Dmochowski
et al., 1993).
With advancing age a persistent insulin resistance along with
the decrease in the circulating insulin levels (due to declining beta cell
function), leads to the onset of glucose intolerance and frank diabetes
mellitus (Chern et al., 2001).
Even in the face of adequate chelation a significant amount of
carbohydrate metabolism dysfunction occurs (Grundy et al., 1994),
suggesting that the development of diabetes might be complicated by other
factors. Pancreatic autoimmunity demonstrated by islet cell antibodies, liver
abnormalities like cirrhosis, liver fibrosis, hepatitis C Infection,
genotype-IVS11nt 745, family history of diabetes are some of the factors
postulated (Suvarna, 2006).
Monge
et al. (2001)
stated that immune system activation against pancreatic β-cells in beta
-thalassemia may result from iron deposition, which through oxidative damage,
acts as an environmental factor that triggers the autoimmune response.
Therefore, pancreatic autoimmunity may contribute to selective beta-cell damage
in the pathogenesis of diabetes associated with beta thalassemia.
Ketoacidosis has been reported to be the presenting
manifestation of diabetes in 13.8% (DeSanctis, 1988), 31.1% of
thalassemics (Chern et al., 2001). To prevent this life
threatening complication active surveillance for the occurrence of impaired
glucose tolerance and diabetes should be carried out in thalassemics especially
in the second decade.
Moreover, thalassemic patients with clinical diabetes are at a
high risk for other complications like endocrine (especially thyroid
dysfunctions) or cardiac or both, and should be strictly monitored for these (De
Sanctis, 1988).
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