OBJECTIVE -To compare the prevalence of diabetes complications and their risk factors in youth with type 1 versus type 2 diabetes.RESEARCH DESIGN AND METHODS -We performed a comparative clinic-based study of 1,433 patients with type 1 diabetes and 68 patients with type 2 diabetes aged Ͻ18 years from New South Wales, Australia. Retinopathy was assessed by seven-field stereoscopic retinal photography; albumin excretion rate from three consecutive, timed, overnight urine collections; peripheral neuropathy by thermal and vibration threshold; and autonomic neuropathy by pupillometry. HbA 1c (A1C) and lipids were measured in all patients and C-peptide in patients with type 2 diabetes.RESULTS -In patients with type 1 versus type 2 diabetes, median (interquartile range) age was 15.7 years (13.9 -17.0) and 15.3 years (13.6 -16.4), respectively (P ϭ 0.2), whereas median diabetes duration was 6.8 years (4.7-9.6) and 1.3 years (0.6 -3.1), respectively (P Ͻ 0.0001). Retinopathy was significantly more common in patients with type 1 diabetes (20 vs. 4%, P ϭ 0.04), while microalbuminuria and hypertension were significantly less common (6 and 16% in type 1 diabetes vs. 28 and 36% in type 2 diabetes). Rates of peripheral and autonomic neuropathy were similar (27 and 61% in type 1 diabetes vs. 21 and 57% in type 2 diabetes). In multivariate analyses, microalbuminuria was significantly associated with older age (odds ratio 1.3 [95% CI 1.2-1.5], P Ͻ 0.001) and systolic hypertension (3.63 [2.0 -6.3], P Ͻ 0.001) in type 1 diabetes, while only higher A1C (1.7 [1.3-2.9], P ϭ 0.002) was significant in patients with type 2 diabetes.CONCLUSIONS -Youth with type 2 diabetes have significantly higher rates of microalbuminuria and hypertension than their peers with type 1 diabetes, despite shorter diabetes duration and lower A1C. The results of this study support recommendations for early complications screening and aggressive targeting of glycemic control in patients with type 2 diabetes. Diabetes Care

OBJECTIVETo examine trends in microvascular complications in adolescents with type 1 diabetes between 1990 and 2009 in Sydney, Australia.RESEARCH DESIGN AND METHODSWe 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.RESULTSRetinopathy 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]).CONCLUSIONSThe decline in retinopathy supports contemporary guidelines that recommend lower glycemic targets and use of MDI/CSII in children and adolescents with type 1 diabetes.

OBJECTIVE -Since the Diabetes Control and Complications Trial, diabetes management goals have changed. The aims of the present study were to assess complication rates, including nerve abnormalities, in adolescents from 1990 to 2002 and to investigate associated risk factors. RESEARCH DESIGN AND METHODS-Cross-sectional analysis of complications was assessed in three study periods (1990 -1994 [T1], 1995-1998 [T2], and 1999 -2002 [T3]) in adolescents matched for age and diabetes duration (n ϭ 878, median age 14.6 years, median duration 7.5 years). Retinopathy was assessed by seven-field stereoscopic fundal photography, albumin excretion rate (AER) from three consecutive timed overnight urine collections, peripheral nerve function by thermal and vibration thresholds, and autonomic nerve function by cardiovascular reflexes.RESULTS -Retinopathy declined significantly (T1, 49%; T2, 31%; and T3, 24%; P Ͻ 0.0001), early elevation of AER (Ն7.5 g/min) declined (38, 30, and 25%, respectively, P ϭ 0.022), and microalbuminuria (AER Ն20 g/min) declined (7, 3, and 3%, respectively; P ϭ 0.017, T1 vs. T2 and T3). Autonomic nerve abnormalities were unchanged (18, 21, and 18%, respectively; P ϭ 0.60), but peripheral nerve abnormalities increased (12, 19, and 24%, respectively; P ϭ 0.0017). More patients were treated with three or more injections per day (12, 46, and 67%, respectively; P Ͻ 0.0001) and insulin dose increased (1.08, 1.17, and 1.22 units ⅐ kg Ϫ1 ⅐ day Ϫ1 , respectively; P Ͻ 0.0001), but median HbA 1c (A1C) was unchanged (8.5, 8.5, and 8.4%, respectively). BMI and height SD score increased: BMI 0.46, 0.67, and 0.79, respectively (P Ͻ 0.0001), and height Ϫ0.09, 0.05, and 0.27, respectively (P Ͻ 0.0001).CONCLUSIONS -Retinopathy and microalbuminuria declined over time in this cohort, but the increased rate of peripheral nerve abnormalities is of concern. Despite intensified management (higher insulin dose and more injections), A1C has not changed and remains well above the recommended targets for adolescents. Recognition that screening is important to identify individuals who will benefit from interventions has led to screening programs for adolescents (2,3). Prevention of long-term chronic complications has now become one of the main goals of modern type 1 diabetes treatment in children and adolescents.In Australia, we initially reported a retinopathy rate of 42% in adolescents (4) and microalbuminuria has been found in 4 -20% of children, mostly after the age of 12-15 years (5-7). Although symptomatic neuropathy is uncommon in children with diabetes, previous studies have found a high prevalence of subclinical neurological abnormalities: nerve conduction abnormalities in 51% (8), cardiac autonomic abnormalities in 31% (9), and reduced sensory sensibility in 16% (10). A decline in the cumulative incidence of nephropathy was reported in Linkoping, Sweden, in 1994 in individuals diagnosed as children during 1961-1980 (11). This finding was considered by some to apply to only that geographical area because a similar study in...

OBJECTIVE—The purpose of this study was to explore whether the presence of thyroid and endomysial autoantibodies at diagnosis of type 1 diabetes in children predicts development of thyroid and celiac disease, respectively, and whether diabetes-associated autoantibodies at diagnosis predict development of microvascular complications up to 13 years later. RESEARCH DESIGN AND METHODS—Autoantibodies were measured at diagnosis of type 1 diabetes in 173 children aged 0–15 years and included thyroperoxidase antibody (TPOA), endomysial antibody (EMA), islet cell autoantibody, GAD antibody (GADA), and insulin autoantibody. Thyroid disease was defined as thyroid stimulating hormone level ≥5 μU/ml. Celiac disease was confirmed by small-bowel biopsy. Assessment of microvascular complications included stereoscopic fundal photography, pupillometry, thermal threshold, and albumin excretion rate (AER). RESULTS—The incidence rates for thyroid and celiac disease were 0.9 and 0.7 per 100 patient-years, respectively. Within 13 years, 6 of 13 children with positive TPOA tests at diagnosis developed thyroid disease compared with 5 of 139 children with negative TPOA tests (P &lt; 0.001). All four patients with positive EMA titers at diagnosis had biopsy-proven celiac disease. Five of 11 patients who developed thyroid disease and 4 of 8 who developed celiac disease had negative TPOA and EMA tests at diagnosis, respectively. Retinopathy was detected in 39% and elevated AER in 36%. The presence of diabetes-associated autoantibodies at diagnosis did not predict microvascular complications though GADA titer levels predicted pupillary abnormality. CONCLUSIONS—Elevated TPOA and EMA levels at diagnosis of type 1 diabetes predict the development of thyroid and celiac disease, respectively. In children with negative antibody titers at diagnosis, screening at 2-year intervals is recommended.

OBJECTIVETo 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 METHODSIn 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.RESULTSRetinopathy 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).CONCLUSIONSVDD 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.

Early retinopathy and elevated AER are common in children 6 years after diagnosis. Initial allied health contact and management at a teaching hospital were associated with a reduced risk of microvascular complications in this cohort.

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. -From 1990-From to 1993, adolescents with type 1 diabetes (n ϭ 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 ϭ 123) and urinary albumin-to-creatinine ratio (n ϭ 99) and retinal (n ϭ 102) screening, as well as analysis of reports from external doctors (n ϭ 35). RESEARCH DESIGN AND METHODSRESULTS -At baseline, there was no difference in age, duration of diabetes, or complications between those who participated in the follow-up phase (n ϭ 137) and those who did not participate (n ϭ 196). However, baseline A1C was lower in the follow-up participants (8.2 vs. 8.5% for participants vs. nonparticipants, respectively, P ϭ 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 ϭ 0.016) and retinopathy (4.83 [1.3-17.98], P ϭ 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. (1) presented a landmark study that reported a predictive relationship between symptomatic autonomic neuropathy and mortality in adults with type 1 diabetes. Deaths 5 years later were predominantly due to associated vascular disease (1), which other authors (2) have considered to be an explanation for the increased mortality related to abnormal cardiac autonomic tests. Deaths were also due to hypoglycemia and "sudden death" (1). Owing to the era of the Ewing et al. study, A1C was not measured; therefore, it was not controlled for, and questions remained unanswered. These questions include whether increased mortality was directly related to glycemic control (i.e., a shared mechanism of damage causing both neuropathy and cardiovascular disease by accumulation of advanced glycation end products) or whether there may be...

No abstract