Plantar fascia thickness is longitudinally associated with retinopathy and renal dysfunction: a prospective study from adolescence to adulthood.

AIM: The aim was to study the longitudinal relationship between plantar fascia thickness (PFT) as a measure of tissue glycation and microvascular (MV) complications in young persons with type 1 diabetes (T1DM). METHODS: We conducted a prospective longitudinal cohort study of 152 (69 male) adolescents with T1DM who underwent repeated MV complications assessments and ultrasound measurements of PFT from baseline (1997-2002) until 2008. Retinopathy was assessed by 7-field stereoscopic fundal photography and nephropathy by albumin excretion rate (AER) from three timed overnight urine specimens. Longitudinal analysis was performed using generalized estimating equations (GEE). RESULTS: Median (interquartile range) age at baseline was 15.1 (13.4-16.8) years, and median follow-up was 8.3 (7.0-9.5) years, with 4 (3-6) visits per patient. Glycemic control improved from baseline to final visit [glycated hemoglobin (HbA1c) 8.5% to 8.0%, respectively; p = .004]. Prevalence of retinopathy increased from 20% to 51% (p < .001) and early elevation of AER (>7.5 µg/min) increased from 26% to 29% (p = .2). A greater increase in PFT (mm/year) was associated with retinopathy at the final assessment (ΔPFT 1st vs. 2nd-4th quartiles, χ(2) = 9.87, p = .02). In multivariate GEE, greater PFT was longitudinally associated with retinopathy [odds ratio (OR) 4.6, 95% confidence interval (CI) 2.0-10.3] and early renal dysfunction (OR 3.2, CI 1.3-8.0) after adjusting for gender, blood pressure standard deviation scores, HbA1c, and total cholesterol. CONCLUSIONS: In young people with T1DM, PFT was longitudinally associated with retinopathy and early renal dysfunction, highlighting the importance of early glycemic control and supporting the role of metabolic memory in MV complications. Measurement of PFT by ultrasound offers a noninvasive estimate of glycemic burden and tissue glycation.

Association between p.Leu54Met polymorphism at the paraoxonase-1 gene and plantar fascia thickness in young subjects with type 1 diabetes.

OBJECTIVE: In type 1 diabetes, plantar fascia, a collagen-rich tissue, is susceptible to glycation and oxidation. Paraoxonase-1 (PON1) is an HDL-bound antioxidant enzyme. PON1 polymorphisms have been associated with susceptibility to macro- and microvascular complications. We investigated the relationship between plantar fascia thickness (PFT) and PON1 gene variants, p.Leu54Met, p.Gln192Arg, and c.-107C>T, in type 1 diabetes. RESEARCH DESIGN AND METHODS: This was a cross-sectional study of 331 adolescents with type 1 diabetes (162 male and 169 female). PFT was assessed by ultrasound, PON1 was assessed by genotyping with PCR and restriction fragment-length polymorphism, and serum PON1 activity was assessed by rates of hydrolysis of paraoxon and phenylacetate. RESULTS: Median (interquartile range) age was 15.4 (13.5-17.3) years, and diabetes duration was 7.6 (4.9-10.6) years. The distribution of p.Leu54Met genotypes was LL 135 (40.8%), ML 149 (45%), and MM 47 (14.2%). PFT was abnormal (>1.7 mm) in 159 adolescents (48%). In multivariate analysis, predictors of abnormal PFT were ML/LL versus MM p.Leu54Met polymorphism (odds ratio 3.84 [95% CI 1.49-9.82], P = 0.005); BMI (percentile) (1.02 [1.01-1.03], P = 0.007); systolic blood pressure (percentile) (1.01 [1.00-1.02], P = 0.03); and male sex (3.29 [1.98-5.46], P < 0.001). CONCLUSIONS: Thickening of the plantar aponeurosis occurs predominantly in overweight and male adolescents with type 1 diabetes. The MM genotype at PON1 p.Leu54Met is associated with a reduced risk of abnormal PFT.

Plantar fascia thickness, a measure of tissue glycation, predicts the development of complications in adolescents with type 1 diabetes.

OBJECTIVE: Direct measurement of collagen glycation requires skin biopsy, which is invasive. We hypothesized that measurement of plantar fascia thickness (PFT) by ultrasound is an alternative index of tissue glycation and a marker of microvascular disease. RESEARCH DESIGN AND METHODS: This was a prospective longitudinal study of microvascular complications in 344 adolescents with type 1 diabetes, whose PFT was assessed by ultrasound at baseline. Retinopathy was assessed by seven-field fundal photography, albumin excretion rate (AER) measured from three consecutive timed overnight urine specimens, autonomic neuropathy by pupillometry and cardiovascular tests, and peripheral neuropathy by vibration and thermal thresholds. Longitudinal analysis was performed using generalized estimating equations with baseline PFT, duration, and A1C as explanatory variables. RESULTS: At first assessment, median (interquartile range) age was 15.1 (13.5-17.2) years and diabetes duration was 8.5 (6.0-11.5) years. Median follow up was 3.2 (2.1-4.5) years with a median of 4 (2-13) complications assessments per patient. In multivariate analysis, baseline PFT (abnormal in 132 subjects, 38%) predicted subsequent development of retinopathy (odds ratio 2.4 [95% CI 1.1-5.0]), elevated AER (2.24 [1.05-5.11]), peripheral neuropathy (2.3 [1.2-4.41]), and autonomic neuropathy (4.94 [2.46-9.91]). Limited joint mobility was present in only 4%. CONCLUSIONS: PFT is a significant predictor of the subsequent development of complications in type 1 diabetes, suggesting that glycation and oxidation of collagen in soft tissues may be independent risk factors for microvascular complications.

High plantar pressure and callus in diabetic adolescents. Incidence and treatment.

This study examined the incidence of high peak plantar pressure and plantar callus in 211 adolescents with diabetes mellitus and 57 nondiabetic controls. The percentage of subjects with these anomalies was the same in both groups. Although diabetic subjects were no more likely than nondiabetic controls to have high peak plantar pressure and callus, these anomalies place individuals with diabetes at greater risk of future foot problems. The effects of orthoses, cushioning, and both in combination were monitored in 17 diabetic subjects with high peak plantar pressure and in 17 diabetic subjects with plantar callus; reductions of up to 63% were achieved. Twelve-month follow-up of diabetic subjects fitted with orthoses showed a significant reduction in peak plantar pressure even when the orthoses were removed. The diabetic subjects who had not received any interventions during the same 12-month period showed no significant change in peak plantar pressure.