Factors determining glucose tolerance in patients with thalassemia major.

To better understand the pathophysiology of glucose intolerance secondary to iron overload in patients with thalassemia major, we performed tolbutamide-modified frequently sampled iv glucose tolerance tests (FSIGTs) in 10 thalassemic patients (6 males and 4 females; 21.7 +/- 1.2 yr old; body mass index, 19.7 +/- 0.6 kg/m2) and 10 healthy controls (5 males and 5 females; 22.4 +/- 1.3 yr; body mass index, 20.6 +/- 0.5 kg/m2). Insulin secretion and action were quantified by application of the minimal model of glucose kinetics and the combined model of insulin and C-peptide kinetics to the FSIGT data. The insulin sensitivity index was significantly lower in thalassemia patients [72 +/- 12 min-1(nmol/mL)] compared to controls [158 +/- 21 min-1(nmol/mL); P = 0.0026]. The integrated insulin response during the FSIGT was significantly greater in thalassemia patients than in controls after tolbutamide injection (P = 0.042). The difference in insulin levels was apparently due to reduced hepatic insulin extraction in thalassemia (78 +/- 2% vs. 68 +/- 3%; P = 0.0251). Seven of the 10 thalassemia patients were studied prospectively at 6-month intervals for 6-12 months. Repeated measures analysis of variance indicated that across a 6-month interval, there was a decrease in the total integrated insulin response (P = 0.002), with no change in insulin sensitivity (P = 0.86). In conclusion, patients with thalassemia major have significant insulin resistance, which may be compensated for by an elevated circulating insulin level. The elevated insulin level in response to tolbutamide appears to be due to reduced hepatic extraction of insulin and not to an enhanced insulin secretory response. Over time, patients with thalassemia experience a reduction in their circulating insulin levels. Persistent insulin resistance along with a progressive reduction in circulating insulin levels may lead to glucose intolerance and diabetes mellitus, which have a high prevalence in patients with thalassemia major.

Serum pancreatic polypeptide and glucagon immunoreactivity in fasting healthy and diabetic children.

Serum pancreatic polypeptide (hPP) concentrations ranged in normal children from 45 pg/ml to 525 pg/ml with mean value at 185 +/- 49 pg/ml. Both hPP and glucagon immunoreactivity (IRG) levels showed age-dependent decrease during childhood. In diabetic children plasma IRG concentrations were significantly increased in comparison with the healthy subjects while hPP concentrations were only slightly elevated. The age dependence of the hormones levels was completely effaced in diabetics. No significant serum hPP norm IRG values dependence on the duration of diabetes was found. IRG/hPP relations correlated with age in healthy children despite those in diabetic ones.

Apparent epidemic of insulin-dependent diabetes mellitus in Midwestern Poland.

There is no information concerning the risk of developing insulin-dependent diabetes mellitus (IDDM) in eastern Europe. An IDDM registry has been developed in Midwest Poland for 1970-1984. The risk of developing IDDM in Polish children was determined through utilization of the registry. The incidence of IDDM in Polish children was very low compared with other Caucasian populations. There was a major increase in risk beginning in 1982; the incidence almost doubled from 3.5/100,000 in 1970-1981 to 6.6/100,000 in 1982-1984. The pattern of IDDM in the high-risk period was different from that in the low-risk period, with an altered seasonal pattern and unusual increased incidence in younger children. The rapid increase in incidence as well as altered epidemiologic patterns during this period suggest that major alterations of environmental factors were responsible for the change in risk.