Risk of nephropathy can be detected before the onset of microalbuminuria during the early years after diagnosis of type 1 diabetes.

Schultz, Carl; Neil, H. A. W.; Dalton, R. Neil; Dunger, David B.

doi:10.2337/diacare.23.12.1811

Cited by 81 publications

(62 citation statements)

References 21 publications

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“…Borderline microalbuminuria at first complication assessment more than doubled the risk of persistent microalbuminuria compared with normoalbuminuria, and the effect persisted after adjusting for duration. This confirms previous studies in which early elevation of AER and the rate of rise of albumin-to-creatinine ratio within the normal range were predictors for microalbuminuria (8,29). While this could be explained by genetic predisposition to nephropathy (30 -32), it argues for the possibility of intervention at a lower level of albuminuria than current guidelines recommended for adolescents (21).…”

Section: Biochemical Subanalysissupporting

confidence: 71%

Natural History and Risk Factors for Microalbuminuria in Adolescents With Type 1 Diabetes

et al. 2006

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OBJECTIVE -To describe the natural history and risk factors for persistent microalbuminuria in children and adolescents with type 1 diabetes followed for up to 15 years. RESEARCH DESIGN AND METHODS-This study contained a longitudinal cohort of 972 patients; analysis of baseline risk factors was performed using logistic regression and predictors over time using survival analysis. Albumin excretion rate was measured on three consecutive timed overnight urine collections on at least two occasions. Normoalbuminuria was defined as a median albumin excretion rate Ͻ7.5 g/min, borderline microalbuminuria as 7.5-20 g/min, and microalbuminuria as 20 -200 g/min. Microalbuminuria was further classified as persistent if its duration was Ͼ12 months. Median age was 12.7 years (interquartile range 11.5-14.4) and diabetes duration 6.5 years (4.1-9.3) at first assessment, and median follow-up was 6.2 years (range 1-15.3).RESULTS -The incidence of persistent microalbuminuria was 4.6 (95% CI 3.3-6.1) per 1,000 patient-years. Predictors of persistent microalbuminuria from the first assessment using multiple logistic regression were high cholesterol (odds ratio 2. CONCLUSIONS -Children and adolescents with type 1 diabetes who have borderline microalbuminuria are more than twice as likely to develop persistent microalbuminuria. In addition to poor glycemic control, clinical markers of insulin resistance were associated with an increased risk of microalbuminuria. Diabetes Care 29:2072-2077, 2006M icroalbuminuria is well recognized as a risk factor for the development of diabetic nephropathy in adults, but its natural history is less clear in children and adolescents. Within 2 decades of diabetes onset, a single episode of microalbuminuria is found in 2-18% of children and adolescents with type 1 diabetes (1-3) but may be transient in up to half of cases (4,5). Established risk factors for microalbuminuria in adolescents and adults include duration of diabetes (5,6), suboptimal glycemic control (7,8), hypertension, and smoking (9).Markers of insulin resistance have been associated with the development of microalbuminuria in adults with type 1 diabetes (10 -14), although there is less evidence for this in children and adolescents. Of note, however, the incidence of microalbuminuria in type 1 diabetes increases at puberty (8), a time of exaggerated physiological insulin resistance (15-17). Indeed, higher androgens and growth hormone have been found in adolescents with type 1 diabetes in association with higher albumin excretion (18,19), while the effects of higher BMI and other features of the metabolic syndrome on the risk of microalbuminuria in this age-group are unclear.The aims of this 15-year longitudinal study were to identify risk factors for early nephropathy and to explore the potential role of insulin resistance in the development of persistent microalbuminuria. We examined putative risk factors at initial assessment for the subsequent development of persistent microalbuminuria and used survival analysis to evaluate risk factors...

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Section: Biochemical Subanalysissupporting

confidence: 71%

Natural History and Risk Factors for Microalbuminuria in Adolescents With Type 1 Diabetes

et al. 2006

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“…Although MA was transient in some of the cases in our study, we recently reported that subjects with persistent MA (2 consecutive years) and transient MA (1 year only) may be at a similar risk of diabetic renal damage, as estimated by the rate of increase of albumin excretion in the years before MA onset (19). Therefore, if a higher systemic BP were important in early renal damage, then the inclusion of subjects with both transient and persistent MA as cases should not have affected the power of our study to detect a BP difference before MA onset.…”

Section: Methodsmentioning

confidence: 90%

Blood Pressure Does Not Rise Before the Onset of Microalbuminuria in Children Followed From Diagnosis of Type 1 Diabetes

Schultz

Ha²,

Rn³

et al. 2001

Diabetes Care

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OBJECTIVE -To examine whether a rise in blood pressure could be detected before the onset of microalbuminuria (MA) in a cohort of children followed from diagnosis of type 1 diabetes. RESEARCH DESIGN AND METHODS -The Oxford Regional ProspectiveStudy is an incident cohort study of children with type 1 diabetes aged (mean Ϯ SD) 9.8 Ϯ 3.7 years at diagnosis. Subjects were assessed annually from diagnosis, with measurement of HbA 1c , arterial blood pressure (random zero), and three urine samples for estimation of the albumin/creatinine ratio. During follow-up, 63 of 494 children developed MA at one or more annual assessments and were designated as cases for a nested case-control study. Each case was matched for sex and age at diagnosis with two normoalbuminuric control subjects. Blood pressure (BP) data were compared at corresponding years of diabetes duration.RESULTS -Cases with MA were similar to normoalbuminuric control subjects with respect to age and BMI, but they had higher mean HbA 1c levels (mean difference 1.1%, P Ͻ 0.001). In the years before the onset of MA, the diastolic BP standard deviation score (SDS) was significantly higher than zero in cases (mean 0.49, P Ͻ 0.001) and in control subjects (0.50, P Ͻ 0.001). No difference could be detected between cases and control subjects before the onset of MA in either systolic or diastolic BP (mean difference systolic Ϫ1.2 mmHg [95% CI Ϫ4.7 to 2.7], mean difference diastolic 0.1 mmHg [Ϫ2.4 to 2.6]). However, within the cases, the onset of MA was associated with elevations in systolic and diastolic BP SDSs (F ϭ 16.1, P Ͻ 0.001; and F ϭ 18.0, P Ͻ 0.001). BMI, but not HbA 1c , was associated with systolic and diastolic BP SDSs in the subjects with MA (F ϭ 0.6, P ϭ 0.4; and F ϭ 12.3, P ϭ 0.001). However, the association of BP with MA remained significant for systolic BP (P ϭ 0.001) and for diastolic BP (P Ͻ 0.001) after adjusting for BMI.CONCLUSIONS -A rise in systemic BP cannot be detected before the first appearance of MA in children with type 1 diabetes. BP rises concurrently with the onset of MA and is also closely related to BMI. Diabetes Care 24:555-560, 2001I n type 1 diabetes, much of the excess morbidity and mortality caused by cardiovascular disease and end-stage renal failure occur in individuals with diabetic nephropathy (1). In addition to hyperglycemia, both environmental factors and a genetic susceptibility are thought to be important factors in the development of diabetic nephropathy (2-4). It is also generally accepted that elevated blood pressure (BP) accelerates the progression of diabetic nephropathy to end-stage renal failure (5), but its role in the pathogenesis of early (incipient) nephropathy is less certain. In recent cross-sectional studies, a familial predisposition to primary hypertension was associated with microalbuminuria (MA) (incipient nephropathy) (6), which suggests that BP may be important in initiating early renal disease. Longitudinal studies that have looked at the temporal relationship of BP and MA onset have not consistently ...

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“…But in children and young adults, albuminuria and overt nephropathy are relatively uncommon. Moreover, several recent studies have reported that microalbuminuria is sometimes reversible (13,19,23). With the exception of one small study (22), the effect of age at onset of diabetes on earlier stages of nephropathy has not been previously reported because investigators have heretofore lacked renal morphometric measures to detect these earlier stages.…”

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confidence: 88%

Effects of Duration and Age at Onset of Type 1 Diabetes on Preclinical Manifestations of Nephropathy

et al. 2003

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Several studies have reported that the effect of type 1 diabetes disease duration on nephropathy may be greater during or after puberty than an equivalent number of years before puberty. The International Diabetic Nephropathy Study examined the effects of disease duration and age at onset on glomerular morphometry obtained from kidney biopsy in 243 young type 1 diabetic subjects with albumin excretion rates <100 g/min: 184 with prepubertal onset, 35 with pubertal onset, and 24 with postpuberty onset. Outcomes included the volume fraction of the glomerulus occupied by the mesangium [Vv(Mes/glom)], glomerular basement membrane (GBM) width, and the surface density of peripheral glomerular capillary basement membrane per glomerulus Sv(PGBM/glom). Vv(Mes/glom) progressed slowly in the first 14 or 15 years after disease onset but more rapidly thereafter. GBM width increased, while Sv(PGBM/glom) decreased with increasing disease duration. No statistically significant differences in the effect of duration were observed among the three age-at-onset subgroups, even with multivariate adjustment for sex, center, baseline HbA 1c concentration, diastolic blood pressure, height, and BMI. Our results may explain the conflicting results of previous studies regarding the effects of pre-versus postpuberty disease duration. Diabetes 52:1818 -1824, 2003 T he microvascular complications of type 1 diabetes are known to increase with duration of the disease (1-4). The results of several studies, however, suggest that the effect of duration on nephropathy and retinopathy may be modified by the age at onset of diabetes and, in particular, that duration after puberty has a larger impact than an equivalent duration before puberty (2,4 -19). The mechanisms proposed to explain this phenomenon include the adverse effects of sex steroids on vascular basement membrane and a deterioration of glycemic control with greater independence from parents during adolescence and young adulthood (5,20,21). The inference that the prepubertal years have little or no effect on the development of diabetes complications could theoretically reduce the aggressiveness of treatment of young children with type 1 diabetes. Nonetheless, the evidence for a lesser effect of prepubertal duration is inconsistent; several studies have yielded conflicting results (2,12,22).Previous studies of pre-versus postpubertal duration effects on diabetic nephropathy have generally used albuminuria as an end point, since albuminuria usually reflects well-established diabetic nephropathy (2,3,5,7,12). But in children and young adults, albuminuria and overt nephropathy are relatively uncommon. Moreover, several recent studies have reported that microalbuminuria is sometimes reversible (13,19,23). With the exception of one small study (22), the effect of age at onset of diabetes on earlier stages of nephropathy has not been previously reported because investigators have heretofore lacked renal morphometric measures to detect these earlier stages. Because albuminuria rarely develops befor...

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Risk of nephropathy can be detected before the onset of microalbuminuria during the early years after diagnosis of type 1 diabetes.

Cited by 81 publications

References 21 publications

Natural History and Risk Factors for Microalbuminuria in Adolescents With Type 1 Diabetes

Natural History and Risk Factors for Microalbuminuria in Adolescents With Type 1 Diabetes

Blood Pressure Does Not Rise Before the Onset of Microalbuminuria in Children Followed From Diagnosis of Type 1 Diabetes

Effects of Duration and Age at Onset of Type 1 Diabetes on Preclinical Manifestations of Nephropathy

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