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Previous studies have demonstrated that limited joint mobility (LJM), the
inability of full digital extension, is increased in children and adolescents
with type 1 diabetes mellitus (T1DM) and relates to poor glycemic control,
age, diabetes duration, and puberty. The data however are very inconsistent
and there are few prospective data. The longitudinal association between LJM,
glycemic control, and microvascular disease has been demonstrated with the
presence of LJM predictive of early retinopathy. Insulin-like growth factor
(IGF)-I levels also have been implicated in the development of microalbuminuria
(MA) and retinopathy. Amin and colleagues described findings in the Oxford
Regional Prospective Study (ORPS) which was established in 1986 and includes
children under the age of 16 years who are assessed annually for height, weight,
blood pressure, urinary albumin:creatinine ratio (ACR) in early morning voids,
HbA1c, and IGF-I. In addition, at the yearly assessments LJM was assessed;
LJM is classified as normal, mild, moderate and severe and the diagnosis was
categorized only if present for 2 or more years. The definition of MA was an
ACR > 3.5 mg/mmol in males and > 4.0 mg/mmol in females. Persistent MA
was defined as ACR above the normal range for 2 or more consecutive years.
One hundred and sixty two subjects with LJM and 301 subjects without LJM
were reported. The median age of first detection of LJM was 13years, reflecting
a median duration of diabetes of 5.2 years; 32.4% developed LJM before puberty.
Mean HbA1c levels were higher in those with LJM, but there were no differences
in HbA1c levels in males without LJM. Subjects with LJM had lower height SDS
and lower mean lifetime height SDS than those without LJM. Mean IGF-I levels
were also lower in the group with LJM. The probability of developing LJM was
related to puberty and HbA1c, but not other variables. In subjects with LJM,
compared to those without LJM, mean ACR levels were higher, but there was no
difference in the prevalence of MA. Following the development of LJM, the probability
of developing MA was related to puberty onset, HbA1c, and female gender. However,
subjects with persistent MA were too few to analyze separately.
The authors stated that their data confirmed those of Rosenbloom’s
group1-3 indicating that LJM is related to poor glycemic control and duration
of diabetes. Subjects with LJM had lower IGF-I levels; the authors previously
reportedthat microalbumin risk is related to low IGF-I levels and growth hormone
hypersecretion, particularly in females.4,5 They pointed out that in rodent
models raised growth hormone induces diabetic neuropathy and chronic hyperglycemia
results in the accumulation of advanced glycation end products with increased
cross-linking in subcutaneous tissues and the formation of inflexible collagen.
In summary, the authors reported that LJM is associated with puberty, independent
of glycemic control, and predictive of MA. Lower IGF-I levels and lower growth
in subjects with LJM may be pathogenetically related.
Amin
R, Bahu TK, Widmer B, Dalton RN, Dunger DB. Longitudinal relation between
limited joint mobility, height, insulin-like growth factor 1 levels, and
risk of developing microalbuminuria: the Oxford Regional Prospective Study.
Arch Dis Child. 2005;90:1039-1044.
Editor’s Comment: The ORPS is a well designed
and carefully followed cohort of children with T1DM. The information which this
group has published regarding the longitudinal changes in a variety of parameters,
particularly growth, IGF-I, and growth hormone secretion, from this cohort have
been valuable additions to the information concerning complications of T1DM in
children and adolescents. The current report of LJM, and its relationship to
low IGF-I and poor growth, is particularly important for readers of GGH. It is
unclear how often LJM is assessed in children with T1DM. Indeed, it appears to
be a painless process and related to, and perhaps predictive of, the development
of MA and retinopathy, and now reduced IGF-I and lower growth velocity. However,
even though the assessment is relatively easy, it cannot replace a careful measurement
of a child’s height, careful fundoscopic exam, and routine and regular
assessment for MA; indeed, the authors did not suggest that such an assessment
be used in that way. LJM is infrequently assessed in pediatric endocrine clinics.
However, because of its relationship to the development of a variety of microvascular
findings, pediatric endocrinologists should be encouraged to perform the simple
assessment, record its presence, and especially utilize this as an important
teaching tool.
William L. Clarke, MD
References - (linked to  )
- Rosenbloom
AL, Silverstein JH, Lezotte DC, Richardson K, McCallum M. Limited joint
mobility in childhood diabetes mellitus indicates increased risk for microvascular
disease.N Engl J Med. 1981;305:191 - 194.
- Rosenbloom
AL, Malone JI, Yucha J, Van Cader TC. Limited joint mobility and diabetic
retinopathy demonstrated by fluorescein angiography. Eur J Pediatr. 1984;141:163
- 164.
- Silverstein
JH, Gordon G, Pollock BH, Rosenbloom AL. Long-term glycemic control
influences the onset of limited joint mobility in type 1 diabetes. J Pediatr.
1998;132:944 - 947.
- Amin
R, Schultz C, Ong K, et al. Oxford Regional Prospective Study. Low
IGF-I and elevated testosterone during puberty in subjects with type 1
diabetes developing microalbuminuria in comparison to normoalbuminuric
control subjects: the Oxford Regional Prospective Study. Diabetes Care.
2003;26:1456 - 1461.
- Amin
R, Williams RM, Frystyk J, et al. 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. Clin Endocrinol (Oxf). 2005;62:137 - 144.
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Current GGH - Vol. 24 No. 1
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