Allison Dart

Earlier onset of complications in youth with type 2 diabetes

OBJECTIVE To evaluate the risk of complications in youth with type 2 diabetes. RESEARCH DESIGN AND METHODS Population-based cohorts of 342 youth (1–18 years of age) with prevalent type 2 diabetes, 1,011 youth with type 1 diabetes, and 1,710 nondiabetic control youth were identified between 1986 and 2007 from a clinical registry and linked to health care records to assess long-term outcomes using ICD-9CM and ICD-10CA codes. RESULTS Youth with type 2 diabetes had an increased risk of any complication (hazard ratio 1.47 [95% CI 1.02–2.12]). Significant adverse clinical factors included age at diagnosis (1.08 [1.02–2.12]), HbA1c (1.06 [1.01–1.12]), and, surprisingly, renin-angiotensin-aldosterone system (RAAS) inhibitor use (1.75 [1.27–2.41]). HNF-1α G319S polymorphism was protective in the type 2 diabetes cohort (0.58 [0.34–0.99]). Kaplan-Meier statistics revealed an earlier diagnosis of renal and neurologic complications in the type 2 diabetes cohort, manifesting within 5 years of diagnosis. No difference in retinopathy was seen. Cardiovascular and cerebrovascular diseases were rare; however, major complications (dialysis, blindness, or amputation) started to manifest 10 years after diagnosis in the type 2 diabetes cohort. Youth with type 2 diabetes had higher rates of all outcomes than nondiabetic control youth and an overall 6.15-fold increased risk of any vascular disease. CONCLUSIONS Youth with type 2 diabetes exhibit complications sooner than youth with type 1 diabetes. Younger age at diagnosis is potentially protective, and glycemic control is an important modifiable risk factor. The unexpected adverse association between RAAS inhibitor use and outcome is likely a confounder by indication; however, further evaluation in young people is warranted.

High Burden of Kidney Disease in Youth-Onset Type 2 Diabetes

OBJECTIVE To evaluate renal outcomes and survival in youth with type 2 diabetes (T2DM) versus type 1 diabetes (T1DM) versus nondiabetic control subjects. RESEARCH DESIGN AND METHODS In total, 342 prevalent youth (aged 1–18 years) with T2DM, 1,011 youth with T1DM, and 1,710 control subjects identified from 1986 to 2007 were anonymously linked to health care records housed at the Manitoba Centre for Health Policy to assess long-term outcomes using ICD codes. RESULTS Youth with T2DM were found to have a fourfold increased risk of renal failure versus youth with T1DM. Risk factors associated with renal failure were renin angiotensin aldosterone system inhibitor use and albuminuria in adolescence. Compared with control subjects (age, sex, and postal code matched), youth with T2DM had a 23-fold increased risk of renal failure and a 39-fold increased risk of dialysis. Kaplan-Meier survival at 10 years was 91.4% in the type 2 diabetic group versus 99.5% in the type 1 diabetic group (P < 0.0001). Renal survival was 100% at 10 years in both groups. It decreased to 92.0% at 15 years and 55.0% at 20 years in the type 2 diabetic group but remained stable in the type 1 diabetic group (P < 0.0001). CONCLUSIONS Youth with T2DM are at high risk of adverse renal outcomes and death. Albuminuria and angiotensin aldosterone system inhibitor use, which may be a marker of severity of disease, are associated with poor outcomes in early adulthood.

Validation of a Pediatric Diabetes Case Definition Using Administrative Health Data in Manitoba, Canada

OBJECTIVE To validate a case definition for diabetes in the pediatric age-group using administrative health data. RESEARCH DESIGN AND METHODS Population-based administrative data from Manitoba, Canada for the years 2004–2006 were anonymously linked to a clinical registry to evaluate the validity of algorithms based on a combination of hospital claim, outpatient physician visit, and drug use data over 1–3 years in youth 1–18 years of age. Agreement between data sources, sensitivity, specificity, negative (NPV) and positive predictive value (PPV) were evaluated for each algorithm. In addition, ascertainment rate of each data source, prevalence, and differences between subtypes of diabetes were evaluated. RESULTS Agreement between data sources was very good. The diabetes definition including one or more hospitalizations or two or more outpatient claims over 2 years provided a sensitivity of 94.2%, specificity of 99.9%, PPV of 81.6% and NPV of 99.9%. The addition of one or more prescription claims to the same definition over 1 year provided similar results. Case ascertainment rates of both sources were very good to excellent and the ascertainment-corrected prevalence for youth-onset diabetes for the year 2006 was 2.4 per 1,000. It was not possible to distinguish between subtypes of diabetes within the administrative database; however, this limitation could be overcome with an anonymous linkage to the clinical registry. CONCLUSIONS Administrative data are a valid source for the determination of pediatric diabetes prevalence that can provide important information for health care planning and evaluation.

Low incidence of adverse events in outpatient pediatric renal allograft biopsies

Abstract:  In 1999, our center implemented a policy of outpatient protocol biopsies as standard practice for the clinical management of pediatric renal allograft recipients. In order to determine the safety of this procedure, we conducted a retrospective chart audit of all outpatient renal allograft biopsies performed at our center. Biopsies were performed under conscious (midazolam) or procedural (propofol/fentanyl) sedation. Localization of the lower pole of the renal allograft was achieved with renal ultrasound. Using a Biopty gun with a 16‐gauge needle, two cores were obtained. Patients were discharged four h post‐biopsy. Patient demographics, hospital length of stay (LOS), specimen adequacy (per Banff criteria) and major and minor adverse events were recorded in a central database. Data were expressed as mean ± SD. From June 1999 to July 2004, we performed 162 biopsies in 43 pediatric renal allograft recipients. Most patients underwent extraperitoneal transplantation (42/43, 97.7%) and were greater than five yr of age at biopsy (129/131 biopsies, 98.5%). The majority of these procedures (131/162, 80.9%) were conducted in the outpatient department, with 113 of 131 (86.3%) being obtained for protocol (n = 89) and one‐month follow‐up acute rejection therapy (n = 24) indications. Patients underwent 3.7 ± 2.7 biopsies (range = 1–11). Specimen adequacy was achieved in 119 of 124 (96.0%) of documented cases. The overall incidence of adverse events was 12 of 131 (9.2%) biopsies, all of which were minor in severity. Macroscopic hematuria was the most common minor adverse event, occurring after 11 of 131 (8.4%) biopsies. While macroscopic hematuria prolonged LOS (adverse events vs. no adverse events: 23.0 ± 26.0 vs. 8.6 ± 4.1 h, p = 0), none of these episodes required major surgical or radiographic interventions. We conclude that in patients greater than five yr of age with extraperitoneal renal allografts, outpatient protocol biopsies using a 16‐gauge needle are sufficiently safe to justify their inclusion in the routine clinical management of pediatric renal allograft recipients and in pediatric clinical trials.

Patterns of chronic injury in pediatric renal allografts.

Background. In pediatric recipients, the pathophysiology of chronic renal allograft injury is poorly understood. Methods. We studied the evolution and determinants of tubulointerstitial, vascular, and glomerular injury in 240 pediatric protocol renal allograft biopsies during the first 5 years posttransplant. Results. Chronic tubulointerstitial injury (ci, ct) developed predominantly during the first 12 months posttransplant, whereas chronic vascular damage (cv, and arteriolar hyalinosis [ah]) and global glomerulosclerosis (gs) became increasingly prevalent at 25 to 36 months and beyond. Chronic interstitial lesions were associated with acute rejection and borderline histology (odds ratio [OR] 2.3, P<0.04), recipient body surface area less than 1.0 m2 (OR 3.6, P<0.05), and obesity (OR 2.0, P<0.03). Determinants of ct were acute rejection (OR 2.6, P=0.02) and acute tubular necrosis (OR 2.8, P<0.04). Vascular fibrous intimal thickening and ah were associated with donor hypertension (OR 3.6, P=0.001) and recipient body surface area less than 1.0 m2 (OR 2.6, P=0.02), respectively. The severity of ah correlated with the incidence of gs (r=0.32, P<0.0001), with 7.8% gs for ah0, 14.3% gs for ah1, 60.0% gs for ah2, and 95.5% gs for ah3 (median values). Antibody induction conferred protection from ci (OR 0.31, P=0.008), ct (OR 0.33, P=0.002), and ah (OR 0.12, P<0.001) progression. Conclusions. By 5 years posttransplant, pediatric renal allografts manifest a substantial burden of tubulointerstitial and microvascular injury. These lesions are associated with donor hypertension, acute inflammation, renal hypoperfusion, obesity, and calcineurin inhibitor toxicity. The pervasiveness and rapid progression of microvascular lesions at 25 to 36 months suggest that attempts at reducing calcineurin inhibitor exposure should be made before two years posttransplant.

Lifestyle Therapy for the Treatment of Youth with Type 2 Diabetes

Type 2 diabetes (T2D) in youth is a relatively novel condition facing paediatric health care providers. Few experimental trials exist to guide clinical management in this population. Supporting and prescribing modifiable lifestyle behaviours is cornerstone in the management of T2D in adults. Clinical trials in obese adolescents suggest that intensive lifestyle interventions that include both dietary changes and increased physical activity elicit clinically meaningful reductions in weight and improve cardiovascular risk profiles. Observational studies in youth with T2D suggest that better diet quality and increased physical activity are associated with better metabolic control; however, the limited experimental data available does not support these observations. Trials evaluating lifestyle monotherapy for the treatment of hyperglycaemia in youth with T2D do not exist, and the only study evaluating combined lifestyle and pharmacologic therapy did not show additional benefit over pharmacologic treatment with metformin alone. Physiological and psychosocial differences between youth and adults with T2D likely contribute to the differences in the effectiveness of lifestyle therapy for improving glycaemic control. The current review describes these topics in detail and provides recommendations for paediatric health care providers for the promotion of lifestyle therapy for the management of hyperglycaemia and cardiovascular risk factors for youth with T2DM.

Canadian Society of Nephrology Commentary on the 2012 KDIGO Clinical Practice Guideline for Glomerulonephritis: Management of Nephrotic Syndrome in Children

The KDIGO (Kidney Disease: Improving Global Outcomes) clinical practice guideline for management of glomerulonephritis was recently released. The Canadian Society of Nephrology convened a working group to review the recommendations and comment on their relevancy and applicability to the Canadian context. A subgroup of pediatric nephrologists reviewed the guideline statements for management of childhood nephrotic syndrome and agreed with most of the guideline statements developed by KDIGO. This commentary highlights areas in which there is lack of evidence and areas in need of translation of evidence into clinical practice. Areas of controversy or uncertainty, including the length of corticosteroid therapy for the initial presentation and relapses, definitions of steroid resistance, and choice of second-line agents, are discussed in more detail. Existing practice variation is also addressed.

Canadian Society of Nephrology Commentary on the 2012 KDIGO Clinical Practice Guideline for Glomerulonephritis: Management of Glomerulonephritis in Adults

The KDIGO (Kidney Disease: Improving Global Outcomes) clinical practice guideline for management of glomerulonephritis was recently released. The Canadian Society of Nephrology convened a working group to review the recommendations and comment on their relevancy and applicability to the Canadian context. A subgroup of adult nephrologists reviewed the guideline statements for management of glomerular disease in adults and agreed with most of the guideline statements developed by KDIGO. This commentary highlights areas for which there is lack of evidence and areas in need of translation of evidence into clinical practice. Areas of controversy or uncertainty, including the choice of second-line agents, are discussed in more detail. Existing practice variation also is addressed. The relevance of treatment recommendations to the Canadian practitioner is discussed.

Standardised Outcomes in Nephrology-Children and Adolescents (SONG-Kids) : a protocol for establishing a core outcome set for children with chronic kidney disease

BackgroundChildren with chronic kidney disease (CKD), requiring dialysis or kidney transplantation, have a mortality rate of up to 30-fold higher than the general aged-matched population, and severely impaired quality of life. Symptoms such as fatigue and pain are prevalent and debilitating. Children with CKD are at risk of cognitive impairment, and poorer educational, vocational, and psychosocial outcomes compared with their well peers, which have consequences through to adulthood. Treatment regimens for children with CKD are long-term, complex, and highly intrusive. While many trials have been conducted to improve outcomes in children with CKD, the outcomes measured and reported are often not relevant to patients and clinicians, and are highly variable. These problems can diminish the value of trials as a means to improve the lives of children with CKD. The Standardised Outcomes in Nephrology—Children and Adolescents (SONG-Kids) study aims to develop a core outcome set for trials in children and adolescents with any stage of CKD that is based on the shared priorities of all stakeholders.Methods/DesignSONG-Kids involves five phases: a systematic review to identify outcomes (both domains and measures) that have been reported in randomised controlled trials involving children aged up to 21 years with CKD; focus groups (using nominal group technique) with adolescent patients and caregivers of paediatric patients (all ages) to identify outcomes that are relevant and important to patients and their family and the reasons for their choices; semistructured key informant interviews with health professionals involved in the care of children with CKD to ascertain their views on establishing core outcomes in paediatric nephrology; an international three-round online Delphi survey with patients, caregivers, clinicians, researchers, policy-makers, and members from industry to develop consensus on important outcome domains; and a stakeholder workshop to review and finalise the set of core outcome domains for trials in children with CKD (including nondialysis-dependent, dialysis, and kidney transplantation).DiscussionEstablishing a core outcome set to be reported in all trials conducted in children with any stage of CKD will enhance the relevance, transparency, and impact of research to improve the lives of children and adolescents with CKD.

Exposure to Gestational Diabetes Mellitus: Impact on the Development of Early-Onset Type 2 Diabetes in Canadian First Nations and Non–First Nations Offspring

OBJECTIVE Type 2 diabetes is increasing in children worldwide, with Canadian First Nations (FN) children disproportionally affected. The prevalence of gestational diabetes mellitus (GDM) also is increasing. The objective of this study was to evaluate the impact of GDM exposure in utero and FN status on the subsequent risk of type 2 diabetes in offspring in the first 30 years of life. RESEARCH DESIGN AND METHODS In this population-based historical prospective cohort study, we used administrative databases linked to a clinical database to explore the independent association and interaction between GDM and FN status on the subsequent development of type 2 diabetes in offspring. RESULTS Among 321,008 births with a median follow-up of 15.1 years, both maternal GDM and FN status were independently associated with subsequent risk of type 2 diabetes in offspring in the first 30 years of life (hazard ratio 3.03 [95% CI 2.44–3.76; P < 0.0001] vs. 4.86 [95% CI 4.08–5.79; P < 0.0001], respectively). No interaction between GDM and FN status on type 2 diabetes risk was observed. FN status had a stronger impact on the development of type 2 diabetes in offspring than GDM. CONCLUSIONS GDM is an important modifiable risk factor for type 2 diabetes, and its prevention may reduce the prevalence of subsequent type 2 diabetes in offspring. This study adds unique and rigorous evidence to the global public health debate about the impact of GDM on the long-term health of offspring.