Stephen Hing

The Effect of Prepubertal Diabetes Duration on Diabetes: Microvascular Complications in Early and Late Adolescence

OBJECTIVE To define the significance of prepubertal diabetes duration in the development of diabetic microvascular complications in adolescents. RESEARCH DESIGN AND METHODS Study A compares complications in 38 prepubertal (PreP) and 140 pubertal (Pub) subjects of the same age (10-14 years) and diabetes duration (3–12 years) to determine if the absence of puberty itself confers a lower risk of complications. Study B examines the importance of prepubertal and pubertal diabetes duration in 193 older adolescents (ages 15–22 years) with prepubertal onset of diabetes. Retinopathy status was assessed using stereoscopic fundus photography of seven fields per eye. Albumin excretion rate (AER) was assessed by three consecutive overnight urine collections, using a polyclonal radioimmunoassay. RESULTS In study A, there were no significant differences between the PreP and Pub groups for retinopathy (27 vs. 29%, P = 0.8) or differences in elevated AER (17 vs. 31%, P = 0.1). In study B, longer prepubertal diabetes duration improved the prediction for retinopathy over postpubertal duration alone (P < 0.0005). No relationship with duration was found for elevated AER (> 7.5, > 15, and > 30 micrograms/min). CONCLUSIONS Prepubertal subjects with diabetes did not have less retinopathy or elevated albumin excretion compared with pubertal subjects of the same age. Prepubertal diabetes duration is significantly related to the presence of retinopathy in adolescents.

Continued Reduction in the Prevalence of Retinopathy in Adolescents With Type 1 Diabetes: Role of insulin therapy and glycemic control

OBJECTIVE To examine trends in microvascular complications in adolescents with type 1 diabetes between 1990 and 2009 in Sydney, Australia. RESEARCH DESIGN AND METHODS We used analysis of complications in 1,604 adolescents (54% female, aged 12–20 years, median duration 8.6 years), stratified by four time periods using Generalized Estimation Equations as follows: T1 (1990–1994), T2 (1995–1999), T3 (2000–2004), and T4 (2005–2009). Early retinopathy was detected using seven-field fundal photography, albumin excretion rate (AER) using timed overnight urine collections, and albumin-to-creatinine ratio (ACR) and peripheral nerve function using thermal and vibration threshold. RESULTS Retinopathy declined (53, 38, 23, and 12%; P < 0.001), as did borderline elevation of AER/ACR (45, 30, 26, and 30%; P < 0.001) and microalbuminuria (8, 4, 3, and 3%; P = 0.006). Multiple daily injections (MDI)/continuous subcutaneous insulin infusion (CSII) use increased (17, 54, 75, and 88%; P < 0.001), median HbA1c decreased (9.1, 8.9, 8.5, and 8.5%; P < 0.001), and severe hypoglycemia was unchanged (6, 8, 10, and 7%; P = 0.272). Retinopathy was associated with diabetes duration (odds ratio [OR] 1.12 [95% CI 1.08–1.17]), age (1.13 [1.06–1.20]), HbA1c (1.16 [1.08–1.25]), systolic blood pressure (BP) SDS (1.31 [1.16–1.48]), socioeconomic disadvantage (1.42 [1.04–1.95]), and 1 to 2 injections per day (vs. MDI/CSII; 1.35 [1.05–1.73]); borderline AER/ACR with male sex (1.32 [1.02–1.70]), age (1.19 [1.12–1.26]), HbA1c (1.18 [1.08–1.29]), weight SDS (1.31 [1.21–1.53]), insulin dose per kilograms (1.64 [1.13–2.39]), 1 to 2 injections per day (1.41 [1.08–1.84]), and socioeconomic disadvantage (1.68 [1.23–2.31]); and microalbuminuria with age (1.14 [1.01–1.29]), HbA1c (1.20 [1.05–1.37]), diastolic BP SDS (1.76 [1.26–2.46]), and 1 to 2 injections per day (1.95 [1.11–3.41]). CONCLUSIONS The decline in retinopathy supports contemporary guidelines that recommend lower glycemic targets and use of MDI/CSII in children and adolescents with type 1 diabetes.

Role of blood pressure in development of early retinopathy in adolescents with type 1 diabetes: prospective cohort study.

Objective To examine the relation between blood pressure and the development of early retinopathy in adolescents with childhood onset type 1 diabetes. Design Prospective cohort study. Setting Diabetes Complications Assessment Service at the Children’s Hospital at Westmead, Sydney, Australia. Participants 1869 patients with type 1 diabetes (54% female) screened for retinopathy with baseline median age 13.4 (interquartile range 12.0-15.2) years, duration 4.9 (3.1-7.0) years, and albumin excretion rate of 4.4 (3.1-6.8) μg/min plus a subgroup of 1093 patients retinopathy-free at baseline and followed for a median 4.1 (2.4-6.6) years. Main outcome measures Early background retinopathy; blood pressure. Results Overall, retinopathy developed in 673 (36%) participants at any time point. In the retinopathy-free group, higher systolic blood pressure (odds ratio 1.01, 95% confidence interval 1.003 to 1.02) and diastolic blood pressure (1.01, 1.002 to 1.03) were predictors of retinopathy, after adjustment for albumin excretion rate (1.27, 1.13 to 1.42), haemoglobin A1c (1.08, 1.02 to 1.15), duration of diabetes (1.16, 1.13 to 1.19), age (1.13, 1.08 to 1.17), and height (0.98, 0.97 to 0.99). In a subgroup of 1025 patients with albumin excretion rate below 7.5 μg/min, the cumulative risk of retinopathy at 10 years’ duration of diabetes was higher for those with systolic blood pressure on or above the 90th centile compared with those below the 90th centile (58% v 35%, P=0.03). The risk was also higher for patients with diastolic blood pressure on or above the 90th centile compared with those below the 90th centile (57% v 35%, P=0.005). Conclusions Both systolic and diastolic blood pressure are predictors of retinopathy and increase the probability of early retinopathy independently of incipient nephropathy in young patients with type 1 diabetes.

Vitamin D deficiency is associated with retinopathy in children and adolescents with type 1 diabetes.

OBJECTIVE To examine the hypothesis that vitamin D deficiency (VDD) is associated with an increased prevalence of microvascular complications in young people with type 1 diabetes. RESEARCH DESIGN AND METHODS In a cross-sectional study of 517 patients, 25-hydroxyvitamin D was measured. Retinopathy was assessed by 7-field stereoscopic retinal photography, peripheral neuropathy by thermal and vibration threshold testing, and microalbuminuria by albumin excretion rate or albumin-to-creatinine ratio. RESULTS Retinopathy prevalence was higher in cases with VDD versus sufficiency (18 vs. 9%, P = 0.02); deficiency was not associated with microalbuminuria or neuropathy. In logistic regression, retinopathy was associated with VDD (odds ratio 2.12 [95% CI 1.03–4.33]), diabetes duration (1.13, 1.05–1.23), and HbA1c (1.24, 1.02–1.50). CONCLUSIONS VDD is associated with an increased prevalence of retinopathy in young people with type 1 diabetes. The inflammatory and angiogenic effects of VDD may contribute to early retinal vascular damage; however, further investigations are warranted.

Prevalence of diabetes complications 6 years after diagnosis in an incident cohort of childhood diabetes

Aims  To examine the prevalence of early diabetes complications 6 years after diagnosis of diabetes. The hypothesis that initial contact with a multidisciplinary team would be associated with a reduced risk of microvascular complications was tested in this cohort.

Autonomic Nerve Testing Predicts the Development of Complications: A 12-year follow-up study

OBJECTIVE—Cardiac autonomic nerve tests have predicted increased mortality in adults with diabetes, predominantly due to nephropathy, cardiac disease, and hypoglycemia. The significance of subclinical autonomic nerve test abnormalities has not been systematically studied in adolescents. We aimed to reassess an adolescent cohort, whose autonomic nervous system had been tested 12 years earlier by both pupillometry and cardiovascular tests. RESEARCH DESIGN AND METHODS—From 1990 to 1993, adolescents with type 1 diabetes (n = 335) were assessed for autonomic neuropathy (median age 14.7 years [interquartile range 13.0–16.8], duration of diabetes 6.3 years [4.0–9.6], and A1C 8.3% [7.5–9.4]). Between 2003 and 2005, contact was made with 59% of the original group. Individual assessment 12 years later included completion of a validated hypoglycemia unawareness questionnaire (n = 123) and urinary albumin-to-creatinine ratio (n = 99) and retinal (n = 102) screening, as well as analysis of reports from external doctors (n = 35). RESULTS—At baseline, there was no difference in age, duration of diabetes, or complications between those who participated in the follow-up phase (n = 137) and those who did not participate (n = 196). However, baseline A1C was lower in the follow-up participants (8.2 vs. 8.5% for participants vs. nonparticipants, respectively, P = 0.031). At 12 years of follow-up, 93% were aware and 7% were unaware that they had hypoglycemia; 32 (31%) had no retinopathy, but 10% required laser therapy, and 80 (81%) had no microalbuminuria. Small pupil size at baseline was independently associated with the development of microalbuminuria (odds ratio 4.36 [95% CI 1.32–14.42], P = 0.016) and retinopathy (4.83 [1.3–17.98], P = 0.019) but not with the development of hypoglycemia unawareness. There was no association with baseline cardiovascular tests and the development of complications 12 years later. CONCLUSIONS—In this study, we found an association between baseline pupillometry tests and the presence of microalbuminuria and retinopathy at 12 years of follow-up. This suggests that pupillometry abnormalities may be early indicators of patients who are at high risk of future microvascular disease.

Secondary glaucoma after paediatric cataract surgery

Aim: To determine the prevalence and risk factors associated with secondary glaucoma postcongenital cataract surgery. Methods: All children diagnosed as having congenital cataracts in a major children’s hospital between 1985 and 2005 were included in a retrospective case series. Medical records of 423 eyes among 283 patients who underwent cataract surgery with or without intraocular lens implantation at age ⩽16 for congenital cataract were reviewed. The main outcome measure was presence or absence of secondary glaucoma and time to glaucoma postsurgery. The following risk factors were evaluated: age at cataract surgery, presence of systemic anomalies, microcornea, persistent hyperplastic primary vitreous (PHPV), primary capsulotomy/anterior vitrectomy, primary intraocular lens implantation, secondary membrane surgery and duration of postoperative observation. Results: The statistical methods were the use of Kaplan–Meier survival analysis and Multivariate Cox hazards regression analysis. The mean follow-up was 6.3 (SD 5.0) years (median 4.6 years; range 0.5 to 20.3 years). Glaucoma developed in 36 of 234 patients (15.4%). Multivariate Cox proportional hazards regression analysis identified age less than 9 months at time of surgery (RR 2.9, 95% CI 1.3 to 7.7; p = 0.03), microcornea (RR 3.7, 95% CI 2.0 to 7.0; p<0.001), and follow-up time as important predictors of glaucoma. PHPV (RR 1.4, 95% CI 0.7 to 2.7; p = 0.41) and primary posterior capsulotomy/anterior vitrectomy (RR 2.2, 95% CI 0.9 to 5.5; p = 0.17) were not significantly associated with secondary glaucoma in the multivariate model. The mean time to glaucoma after congenital cataract surgery was 4.9 years (range 2 weeks to 16.8 years). Conclusion: Secondary glaucoma is an important sequela in patients who undergo surgery for congenital cataracts. It is imperative that these patients get lifelong surveillance, as glaucoma can occur years after the initial operation.

Microvascular complications assessment in adolescents with 2- to 5-yr duration of type 1 diabetes from 1990 to 2006

Cho YH, Craig ME, Hing S, Gallego PH, Poon M, Chan A, Donaghue KC. Microvascular complications assessment in adolescents with 2‐ to 5‐yr duration of type 1 diabetes from 1990 to 2006.

Association Between HbA1c Variability and Risk of Microvascular Complications in Adolescents With Type 1 Diabetes

CONTEXT There is a paucity of data regarding the association between glycosylated hemoglobin (HbA1c) variability and risk of microvascular complications in adolescents with type 1 diabetes (T1D). OBJECTIVE To investigate the association between HbA1c variability and risk of microvascular complications in adolescents with T1D. DESIGN Prospective cohort study from 1990 to 2014 (median follow-up, 8.1 y). SETTING Tertiary pediatric hospital. PARTICIPANTS A total of 1706 adolescents (aged 12-20 minimum diabetes duration 5 y) with median age of 15.9 years (interquartile range, 14.3-17.5) and diabetes duration of 8.1 years (6.3-10.8). MAIN OUTCOME MEASURES Glycemic variability was computed as the SD of all HbA1c measurements (SD-HbA1c) after diagnosis. Retinopathy was detected using 7-field fundal photography, renal function assessed using albumin excretion rate, peripheral neuropathy detected using thermal and vibration threshold testing, and cardiac autonomic neuropathy (CAN) detected using time- and frequency-domain analyses of electrocardiogram recordings. Generalized estimating equations were used to examine the relationship between complications outcomes and HbA1c variability, after adjusting for known risk factors, including HbA1c, diabetes duration, blood pressure, and lipids. RESULTS In multivariable analysis, SD-HbA1c was associated with early retinopathy (odds ratio [OR] 1.32; 95% confidence interval, 1.00-1.73), albuminuria (OR 1.81; 1.04-3.14), increased log10 albumin excretion rate (OR 1.10; 1.05-1.15) and CAN (OR 2.28; 1.23-4.21) but not peripheral neuropathy. CONCLUSIONS Greater HbA1c variability predicts retinopathy, early nephropathy, and CAN, in addition to established risk factors, in adolescents with T1D. Minimizing long term fluctuations in glycemia may provide additional protection against the development of microvascular complications.

Early elevation of albumin excretion rate is associated with poor gluten-free diet adherence in young people with coeliac disease and diabetes

There are conflicting data on microvascular complications in coexisting Type 1 diabetes and coeliac disease. We compared complications rates in youth with or without coeliac disease and examined the association between gluten‐free diet adherence and complications.