Prepubertal Duration Of Diabetes Research Articles

Clinical and epidemiological characteristics of diabetic nephropathy in children and adolescents in Moscow with insulin-dependent diabetes mellitus

A total of 166 patients (72 males and 94 females) with insulindependent diabetes mellitus (IDDM) aged 5 to 21 years with disease duration of 1 to 18 years were examined in order to assess the clinical picture and epidemiology of diabetic nephropathy (DN) in children and adolescents in Moscow. Microalbuminuria (MAU)*was the criterion of DN. DN was diagnosed in 75 (45.7%) of patients: in 64 (85.3%) at the MAU stage and in 11 (14.6%)) at the stage of proteinuria. There were no cases with the nephrotic syndrome or chronic renal insufficiency. The minimal duration of IDDM in adolescents with MAU was about 2 years, in those with proteinuria about 5 years. All patients with DN were pubertal or postpubertal. The incidence of DN did not depend on the sex, age, or pubertal status. DN risk factors in these patients were chronic hyperglycemia, total and prepubertal duration of diabetes, hereditary predisposition to arterial hypertension, and lipid disorders. Therefore, prepubertal children with disease duration of 5 years and adolescents with disease duration of 1 year since IDDM manifestation are to be screened for DN.

Infant and Toddler Type 1 Diabetes

OBJECTIVETo compare the effect of the prepubertal duration of diabetes on the occurrence of complications in two groups of patients after the same number of years of the disease.RESEARCH DESIGN AND METHODSThis multicenter study enrolled 105 patients aged 16–40.3 years; 53 were prepubertal at diagnosis (aged 0–3) and 52 were pubertal (Tanner stage) and aged 9–14.9. The mean duration of disease was 19.8 and 19.5 years for prepubertal and pubertal patients, respectively. In all patients, retinal photographs were taken and centrally graded. Urinary albumin excretion (UAE; 86 case subjects), blood pressure (BP; 89 case subjects), and lifetime HbA1c (72 case subjects) were also evaluated.RESULTSThe prevalence of diabetic retinopathy (DR) was higher in pubertal than in prepubertal patients, both for any grade DR (71 vs. 40%, P = 0.002) and for mild or more severe DR (P = 0.005). The prevalence of abnormal UAE was not different in the two groups. Hypertension was found only in three patients, all pubertal at diagnosis. In the small group with moderate-to-severe DR, lifetime HbA1c levels, as percentages above the upper normal reference value, were higher (P < 0.01) in prepubertal than in pubertal patients.CONCLUSIONSIf diabetes is diagnosed in infants or toddlers and the prepubertal duration of diabetes is very long, the patients seem to be protected against DR. This protection disappears if lifetime metabolic control is bad. Instead, when onset is at puberty, the DR risk is higher and less dependent on metabolic control and may be influenced by age-related factors, such as BP.

Contribution of sex hormones in the progression of diabetic microvascular diseases.

Contribution of sex hormones in the progression of diabetic microvascular diseases.

The significance of the prepubertal diabetes duration for the development of retinopathy and nephropathy in patients with type 1 diabetes

Objective: A Danish nationwide prospective cohort of children and adolescents with type 1 diabetes was followed for 8 years to study the effect of the prepubertal duration of diabetes on early retinopathy and elevated albumin excretion rate (AER) (>20 μg/min). Research Design and Methods: In 1989, blood glucose control (HbA1c) and AER was investigated in approximately 80% of all Danish children and adolescents with type 1 diabetes. A cohort of 339 young patients were restudied in 1995 including physical examination, demographic data, HbA1c, AER, and fundus photography with central reading. Among the patients, a number of 304 had a prepubertal onset of diabetes defined as an onset age less than 11.7 years in girls and 12.9 years in boys. Microalbuminuria was defined as an AER of 20–150 μg min−1 and macroalbuminuria as AER >150 μg min−1 in two out of three timed overnight urine samples. Results: At the follow-up in 1995–1996, no patients were younger than 12 years of age. The prevalence of any level of retinopathy was 17.7% in the age group 12–15 years, 45.4% from 16 to 20 years, and increased to 67.6% in patients more than 20 years of age. Diabetic retinopathy was significantly associated to poor long-term metabolic control (HbA1c) (P<.0001) and to diabetes duration both in patients with a prepubertal onset of disease as well as patients with a pubertal (P<.001) onset of disease. However, the pubertal diabetes duration contributed two times more than the prepubertal diabetes duration. Mean postpubertal diabetes duration to any retinopathy was significantly shorter (9.4 years) in patients with prepubertal onset of the disease compared to patients with postpubertal onset (11.8 years) (P=.0004). In total, the prevalence of elevated AER (>20 μg/min) increased from 4% in 1989 to 13% in 1995. None of the patients younger than 15 years of age had elevated AER, while the prevalence of elevated AER was about 14% from 15 years of age and onwards. Elevated AER in 1995 was significantly related to long-term metabolic control (P<.001) and elevated AER in the preceding years (P<.001) but was not correlated to diabetes duration neither before nor after the age of 12 years. Conclusion: The prepubertal diabetes duration is significantly associated with the development of diabetic retinopathy. The period, however, contributes less compared to the years after puberty. In concert with other studies, we found no association between raised AER and diabetes duration. This may be explained by the fact that other factors are more significant and dilute the significance of diabetes duration. Nonetheless, it seems prudent to optimise blood glucose control irrespective of age.

Urinary excretion of albumin in adolescents with type 1 diabetes: persistent versus intermittent microalbuminuria and relationship to duration of diabetes, sex, and metabolic control.

Urinary excretion of albumin is a marker for incipient diabetic nephropathy in adults. The intra-individual variability, as well as the relationship to duration of diabetes, onset of the disease, and long-term metabolic control, have not been evaluated in a large sample of pediatric patients. A total of 5,722 nocturnal urinary albumin excretion rates were determined in 447 children, adolescents, and young adults with type 1 diabetes, comprising 1,821 years of observation. Excretion rates were related to duration of diabetes, age at onset of diabetes, sex, blood pressure, and metabolic control. Based on repeated measurements in individual patients, the positive predictive value of one sample was 76%, the negative 99.5%. After a duration of diabetes of 11 years, 5% of patients displayed persistent microalbuminuria (10% after 13 years). The duration of diabetes until persistent microalbuminuria was identical for patients with prepubertal or pubertal onset of diabetes. In addition to duration, female sex (P < 0.03) and insufficient long-term metabolic control (P < 0.03) contributed significantly and independently to urinary albumin excretion. Determination of urinary albumin excretion rate is useful in pediatric patients. Female subjects with a long duration of diabetes and insufficient metabolic control are especially at risk for microalbuminuria. Even if persistent microalbuminuria usually becomes evident in patients aged > 11 years, the prepubertal duration of diabetes contributes equally to this risk. Good metabolic control therefore should be aspired to from the onset of diabetes.

Microalbuminuria prevalence varies with age, sex, and puberty in children with type 1 diabetes followed from diagnosis in a longitudinal study. Oxford Regional Prospective Study Group.

The predictive value of microalbuminuria (MA) in children with type 1 diabetes has not been defined. We describe the natural history of MA in a large cohort of children recruited at diagnosis of type 1 diabetes. Between 1985 and 1996, 514 children (279 male) who developed type 1 diabetes before the age of 16 years (91% of those eligible from a region where ascertainment of new cases is 95%) were recruited for a longitudinal study with central annual assessment of HbAlc and albumin excretion (three urine samples). Dropout rates have been < 1% per year, and 287 children have been followed for > 4.5 years. MA (defined as albumin-to-creatinine ratio > or = 3.5 and > or = 4.0 mg/mmol in boys and girls, respectively) developed in 63 (12.8%) and was persistent in 22 (4.8%) of the subjects. The cumulative probability (based on the Kaplan-Meier method) for developing MA was 40% after 11 years. HbAlc was worse in those who developed MA than in others (mean difference +/- SEM: 1.1% +/- 0.2, P < 0.001). In subjects who had been 5-11 years of age when their diabetes was diagnosed, the appearance of MA was delayed until puberty, whereas of those whose age was < 5 years at diagnosis of diabetes, 5 of 11 (45%) developed MA before puberty. The adjusted proportional probability (Cox model) of MA was greater for female subjects (200%), after pubertal onset (310%), and with greater HbAlc (36% increase for every 1% increase in HbAlc). Despite earlier differences based on age at diagnosis of diabetes (< 5, 5-11, and > 11 years), the overall cumulative risks in these groups were similar (38 vs. 29 vs. 39%, respectively) after 10 years' duration of diabetes. Prepubertal duration of diabetes and prepubertal hyperglycemia contribute to the risk of postpubertal MA. The differences in rates of development of MA relating to HbAlc, sex, and age at diagnosis relative to puberty may have long-term consequences for the risk of subsequent nephropathy and for cardiovascular risk.

The development and progression of diabetic retinopathy in type I diabetic patients: a cohort study

To describe the course and risk factors for development and progression of retinopathy, we studied a cohort of 333 Israeli Jewish patients with Type 1 (insulin-dependent) diabetes mellitus. The median age at diagnosis was 9.5 (range 0.04–26.2) years and the median duration of follow-up was 14 (range 1.6–30) years. Evaluation of both retinae was performed yearly since referral and HbA1 values were tested every 3 months since 1978. During a follow-up of 4070 patient-years, 162 patients developed non-proliferative retinopathy. The median retinopathy-free interval was 14.9 years and after 30 years all patients were affected. Pre-pubertal duration of diabetes was relevant. Independent and significant risk factors for early onset of non-proliferative retinopathy were: poor cumulative glycaemic control (median retinopathy-free interval in the 1st vs 4th quartiles of mean HbA1 values over all years: 18.0 vs 12.5 years, p = 0.0001); onset of diabetes during or after puberty (median retinopathy-free interval in patients with onset of diabetes before, during or after pubescence: 16.3, 13.2 and 14.0 years, respectively, p = 0.0001); and non-Ashkenazi Jewish origin (median retinopathy-free interval 15.8 years in Ashkenazi vs 14.0 in non-Ashkenazi patients, p = 0.0004). Of 162 patients with non-proliferative retinopathy, progression to proliferative retinopathy occurred in 37, during 707 patient-years. The first event of proliferative retinopathy was diagnosed within the 1st year after non-proliferative retinopathy evolved, and at 6.3 years since onset of non-proliferative retinopathy 75 % of the patients were still free of proliferative changes. Risk factors significantly and independently associated with an early progression to the proliferative stage were: poor glycaemic control in the last 3 years prior to the development of proliferative retinopathy and non-Ashkenazi Jewish origin. All patients in the 4th quartile of HbA1 values were affected by proliferative retinopathy within 11.6 years after onset of non-proliferative retinopathy. © 1997 John Wiley & Sons, Ltd.

The development and progression of diabetic retinopathy in type I diabetic patients: a cohort study.

To describe the course and risk factors for development and progression of retinopathy, we studied a cohort of 333 Israeli Jewish patients with Type 1 (insulin-dependent) diabetes mellitus. The median age at diagnosis was 9.5 (range 0.04-26.2) years and the median duration of follow-up was 14 (range 1.6-30) years. Evaluation of both retinae was performed yearly since referral and HbA1 values were tested every 3 months since 1978. During a follow-up of 4070 patient-years, 162 patients developed non-proliferative retinopathy. The median retinopathy-free interval was 14.9 years and after 30 years all patients were affected. Pre-pubertal duration of diabetes was relevant. Independent and significant risk factors for early onset of non-proliferative retinopathy were: poor cumulative glycaemic control (median retinopathy-free interval in the 1st vs 4th quartiles of mean HbA1 values over all years: 18.0 vs 12.5 years, p = 0.0001); onset of diabetes during or after puberty (median retinopathy-free interval in patients with onset of diabetes before, during or after pubescence: 16.3, 13.2 and 14.0 years, respectively, p = 0.0001); and non-Ashkenazi Jewish origin (median retinopathy-free interval 15.8 years in Ashkenazi vs 14.0 in non-Ashkenazi patients, p = 0.0004). Of 162 patients with non-proliferative retinopathy, progression to proliferative retinopathy occurred in 37, during 707 patient-years. The first event of proliferative retinopathy was diagnosed within the 1st year after non-proliferative retinopathy evolved, and at 6.3 years since onset of non-proliferative retinopathy 75% of the patients were still free of proliferative changes. Risk factors significantly and independently associated with an early progression to the proliferative stage were: poor glycaemic control in the last 3 years prior to the development of proliferative retinopathy and non-Ashkenazi Jewish origin. All patients in the 4th quartile of HbA1 values were affected by proliferative retinopathy within 11.6 years after onset of non-proliferative retinopathy.

PREPUBERTAL HYPERGLYCEMIA CAUSES NERVE DAMAGE. † 538

It has been reported that prepubertal duration of diabetes has a minimal influence on the later risk of diabetic complications. Rats made hyperglycemic at 6 weeks of age (before puberty) manifest reduced nerve conduction velocity(NCV) by 10 weeks of age and show morphologic differences in the sciatic tibial nerve after 5 months of hyperglycemia when compared to age matched controls. Fiber diameter, myelin width, and the number of large myelinated fibers (> 6.5 um) were decreased. The number of small (< 6.5 um) developing myelinated fibers were increased. Rats made hyperglycemic at 26 weeks of age (post pubertal) had elevated glycosylated hemoglobin and sciatic nerve sorbitol but maintained normal NCVs and had little change in morphology after 7 months of hyperglycemia. Thus, animals with maturing peripheral nerve structure and function (characteristic of the prepubertal period) exposed to chronic hyperglycemia manifest greater pathologic alterations than occur when more mature nerves are exposed to similarly elevated glucose concentrations for an even greater duration. This suggests that growing maturing tissues of prepubertal children may be more sensitive to the toxic effects of hyperglycemia than mature adult tissues. In summary, the tissues of prepubertal animals are not immune to the toxic effects of hyperglycemia. Blood glucose control is likely to be important for the normal maturation of tissues in prepubertal children with diabetes mellitus.

Prevalence and risk factors for retinopathy in adolescents with type 1 diabetes.

To establish the prevalence of, and risk factors associated with, diabetic retinopathy in an Australian adolescent diabetes clinic population. A prospective longitudinal study; baseline findings. Two hundred and fifty-five patients with Type 1 (insulin-dependent) diabetes mellitus assessed by our service were studied. Entry criteria were: age 11.0-19.9 years; diabetes duration of at least two years; and gradable fundus photographs of at least one eye. The presence and severity of retinopathy, as assessed by the grading of stereoscopic fundus photographs. Possible risk factors assessed were age, sex, diabetes duration, pubertal stage, blood pressure, glycaemic control and total cholesterol level. The prevalence of retinopathy was 42%; all of those affected had mild background retinopathy. Highly significant associations were found with glycaemic control and both total and prepubertal duration of diabetes. No associations were found with age, sex, pubertal stage, blood pressure or total cholesterol level. The high prevalence of early diabetic retinopathy in this group of Australian adolescents is comparable to recent reports from other centres. The significant associations with glycaemic control and duration of diabetes provide further strong evidence for the benefit of optimal glycaemic control during adolescence. Our finding that the prepubertal years of diabetes contribute to the development of retinopathy suggests that glycaemic control before puberty should also be optimised. The planned follow-up of this cohort will establish the risk of progression to vision-threatening retinopathy and allow risk factors to be further evaluated.

Glycemic Control and Development of Retinopathy in Youth-onset Insulin-dependent Diabetes Mellitus: Results of a 12-year Longitudinal Study

In 1979, the authors began a prospective study of the natural history of retinopathy in youth-onset insulin-dependent diabetes mellitus (IDDM). Their major goal was to determine if there was an association between glycemic control and the development and progression of retinopathy. The study consisted of 420 individuals with IDDM (onset younger than 20 years of age) and no retinopathy at baseline. Study subjects were enrolled between 1979 and 1988. Stereo color fundus photographs were obtained annually. Two eye endpoints were recorded: duration when retinopathy was first detected, and when proliferative retinopathy was detected. Glycemic control was assessed by quarterly determinations of glycohemoglobin (GHb). Life-table analyses were performed relating duration of diabetes, sex, GHb, and age of diabetes onset to development of retinopathy. Retinopathy did not develop before 2 years' duration or before puberty. The prevalence of retinopathy was 50% by 9 years' duration and 100% by 20 years' duration. Retinopathy developed in females approximately 2 years sooner than in males, but plotting duration as postpubertal years resulted in nearly identical rates. Retinopathy developed significantly earlier in subjects with prepubertal onset of diabetes than in subjects with postpubertal onset if duration was plotted as postpubertal years. When separated into three groups based on GHb levels (< 7.5%, 7.5%-9%, > 9%), retinopathy developed approximately 2 years later in subjects in the less than 7.5% GHb group than those in the higher GHb groups. Proliferative retinopathy developed in 11 subjects. Their mean GHb level was higher than the mean GHb for those without proliferative retinopathy (10.9 versus 8.6%; P < 0.01). The higher the level of GHb, the sooner proliferative changes were detected. Long-term glycemic control is significantly related to both development and progression of retinopathy. Prepubertal duration of diabetes is a significant risk factor for the development of retinopathy.

Plasma renin activity and albumin excretion in teenage type I diabetic subjects. A prospective study.

Plasma renin activity (PRA) may be high among teenage and young adult insulin-dependent diabetic subjects. Supine PRA and stimulated PRA were therefore measured in 50 female and 50 male diabetic subjects, 13-20 years old, diagnosed before the age of 16. Fifty percent have been restudied after 4.6 +/- 0.2 (mean +/- SEM) years. Initially, 43% had high PRA (supine 4.0 +/- 0.37, stimulated 12.02 +/- 0.8 ng/ml/hr angiotensin I), 45% had normal activity (supine 2.89 +/- 0.26, stimulated 6.47 +/- 0.34 ng/ml/hr/angiotensin I), and 12% had low activity (supine 1.57 +/- 0.05, stimulated 3.09 +/- 0.08 ng/ml/hr/angiotensin I). Levels were directly associated with prepubertal duration of diabetes and were inversely associated with duration of diabetes after onset of puberty but not with total duration or patient age. Within 4.6 +/- 0.2 years the percentage of subjects with high PRA fell to 13%, and the percentage of those with low PRA rose to 35%. Initially 51% of the cohort had normal albumin excretion rates (AER) at rest and during exercise equal to or less than 10 micrograms/min/m2; 32% had elevated rates only during exercise of 39 +/- 5 micrograms/min/m2; 13% had elevated rates at rest of 41 +/- 8 micrograms/min/m2 and during exercise of 116 +/- 21 micrograms/min/m2; and 4% had clinical proteinuria at rest and during each exercise period equal to or greater than 150 micrograms/min/m2. After 5 years, 58% continued to have normal AER, or their AER improved.(ABSTRACT TRUNCATED AT 250 WORDS)