Table of Contents 22-1

Joint Mobility and Type 1 Diabetes Complications

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 group^1-3 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 )

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.