Increasing urine albumin excretion is associated with growth hormone hypersecretion and reduced clearance of insulin in adolescents and young adults with type 1 diabetes: the Oxford Regional Prospective Study.
OBJECTIVE
We previously described lower insulin-like growth factor I (IGF-I) levels in association with increased microalbuminuria (MA) risk in type 1 diabetic subjects followed from diabetes diagnosis through puberty into adulthood. By inference lower IGF-I levels may be associated with higher GH levels and changes in insulin sensitivity.


METHODS
To test this hypothesis, microalbuminuric subjects (MA+, n = 14) from the same cohort had overnight GH levels measured during euglycaemia (5 mmol/l, 01:00-07:30 h) maintained by a variable rate insulin infusion followed by a 2-step hyperinsulinaemic, euglycaemic clamp study using [6.6 2H2] glucose, and were compared to MA- controls (MA-, n = 14), matched for age (median 19.3 years, range 15.8-30.5), sex, duration of diabetes (11.1 years, range 5.1-16.4).


RESULTS
In MA+ cases GH levels, measured by the Pulsar programme, were higher (baseline; 1.8 +/- 1.4 vs. 0.7 +/- 0.5 ng/ml, P = 0.02, mean; 3.8 +/- 1.3 vs. 2.6 +/- 1.6 ng/ml, P = 0.03, maximum; 16.7 +/- 7.0 vs. 12.3 +/- 5.4, P = 0.02), despite similar HbA1(c) levels (9.8%vs. 9.6%, P = 0.6) and body or truncal fat mass. Fourier transform revealed increased GH pulse amplitude at all periodicities and overnight insulin clearance was reduced (11.7 +/- 6.9 vs. 20.1 +/- 6.5 ml/kg/min, P < 0.02). In multiple regression analysis, urine albumin excretion was associated with higher GH levels and reduced insulin clearance, independent of HbA1(c) and body composition. In female cases (n = 9), dextrose requirements were reduced during the first step of the euglycaemic clamp (1.7 +/- 0.8 vs. 2.7 +/- 1.4, P < 0.05) but no such differences existed in males or in the rate of glucose production or disposal.


CONCLUSIONS
The development of MA during puberty and young adulthood is associated with higher GH levels and abnormalities in insulin metabolism, particularly in females. These data extend support for our previous findings indicating a role for the GH/IGF-I axis in the pathogenesis of MA.
Amin
Rakesh
R
University Department of Paediatrics, Addenbrookes Hospital, Cambridge, UK.
Williams
Rachel M
RM
Frystyk
January
J
Umpleby
Margot
M
Matthews
David
D
Orskov
Hans
H
Dalton
R Neil
RN
Dunger
David B
DB
D000293:Adolescent; D000328:Adult; D000419:Albuminuria / Q000097:blood / Q000209:etiology*; D016022:Case-Control Studies; D003404:Creatinine / Q000652:urine; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000652:urine*; D005260:Female; D005583:Fourier Analysis; D005951:Glucose Tolerance Test; D013006:Growth Hormone / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000097:blood; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D011446:Prospective Studies; D012737:Sex Factors
D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D003404:Creatinine