The effect of renal hyperfiltration on urinary inflammatory cytokines/chemokines in patients with uncomplicated type 1 diabetes mellitus.

AIMS/HYPOTHESIS: High intraglomerular pressure causes renal inflammation in experimental models of diabetes. Our objective was to determine whether renal hyperfiltration, a surrogate for intraglomerular hypertension, is associated with increased excretion of urinary cytokines/chemokines in patients with type 1 diabetes mellitus. METHODS: Blood pressure, renal haemodynamic function (inulin and para-aminohippurate clearances for glomerular filtration rate (GFR) and effective renal plasma flow (ERPF), respectively) and urine samples were obtained during clamped euglycaemia in individuals with type 1 diabetes with either hyperfiltration (GFR determined using inulin [GFRINULIN] ≥ 135 ml min⁻¹ 1.73 m⁻², n = 28) or normofiltration (n = 21) and healthy control individuals (n = 18). RESULTS: Baseline clinical characteristics, dietary sodium and protein intake and blood pressure levels were similar in the diabetic and healthy control groups. In addition, HbA1c levels were similar in the two diabetic groups. As expected baseline GFR was higher in hyperfilterers than either normofiltering diabetic patients or healthy control patients (165 ± 9 vs 113 ± 2 and 116 ± 4 ml min⁻¹ 1.73 m⁻², respectively, p < 0.01). ERPF and renal blood flow were also comparatively higher and renal vascular resistance was lower in hyperfiltering patients (p < 0.01). Hyperfiltering diabetic patients had higher excretion rates for eotaxin, IFNα2, macrophage-derived chemokine, platelet-derived growth factor (PDGF)-AA, PDGF-AB/BB and granulocyte-macrophage colony-stimulating factor (p ≤ 0.01). Urinary monocyte chemoattractant protein (MCP)-1 and RANTES (regulated on activation, normal T expressed and secreted) excretion was also higher in hyperfiltering vs normofiltering diabetic individuals (p < 0.01) and fibroblast growth factor-2, MCP-3 and CD40K excretion was elevated in hyperfiltering diabetic individuals vs healthy controls (p < 0.01). CONCLUSIONS/INTERPRETATION: Renal hyperfiltration is associated with increased urinary excretion of inflammatory cytokines/chemokines in patients with uncomplicated type 1 diabetes.

Ability of cystatin C to detect acute changes in glomerular filtration rate provoked by hyperglycaemia in uncomplicated Type 1 diabetes.

AIMS: Systematic study of hyperfiltration in diabetic nephropathy has been hindered by the lack of a simple glomerular filtration rate (GFR) measure that is accurate in this range of renal function. Serum cystatin C (GFR(CYSTATIN C) ) reflects long-term trends in GFR in normal or elevated ranges. To test whether it can reflect acute changes, we examined the impact of clamped hyperglycaemia on GFR(CYSTATIN C) and GFR(INULIN) in subjects with Type 1 diabetes. METHODS: GFR(INULIN) and GFR(CYSTATIN C) were measured in 32 normotensive, normoalbuminuric subjects during clamped euglycaemia and hyperglycaemia. For comparison, GFR(MDRD) was estimated according to the four-variable equation. RESULTS: During clamped euglycaemia, agreement between GFR(CYSTATIN C) and GFR(INULIN) was excellent, with mean bias +1.9 (90% distribution -29 to +31) ml min(-1) 1.73 m(-2), while GFR(MDRD) had mean bias +11.4 (-45 to +51) ml min(-1) 1.73 m(-2). With exposure to clamped hyperglycaemia, the mean increase in GFR(CYSTATIN C) (+17.5 ± 13.5 ml min(-1) 1.73 m(-2) ) reflected that observed with GFR(INULIN) (+15.3 ± 28.1 ml min(-1) 1.73 m(-2), P = 0.74), while GFR(MDRD) demonstrated a mean decline of -4.4 ± 33.6 ml min(-1) 1.73 m(-2) (P = 0.01). In all 24 subjects in whom GFR(INULIN) increased in response to hyperglycaemia, GFR(CYSTATIN C) reflected a concordant change (sensitivity, 100%) while GFR(MDRD) increased in 10/24 (sensitivity, 42%). In the eight remaining subjects, specificity was 25 and 75% for GFR(CYSTATIN C) and GFR(MDRD), respectively. CONCLUSION: GFR(CYSTATIN C) reflects normal and elevated renal function better than GFR(MDRD) even under the acute influences of hyperglycaemia, suggesting a role for cystatin C in clinical practice and research for the study of early renal function changes in Type 1 diabetes.

Bone health in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED): findings in 25 adults.

OBJECTIVE: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is characterized by chronic mucocutaneous candidiasis and autoimmune destruction of endocrine organs. The resulting endocrinopathies and their treatment may impact bone health. The purpose of our study was to assess bone health and its correlates in adult patients with APECED. PATIENTS AND METHODS: Twenty-five adults (12 males) with APECED were prospectively assessed. Data on their previous medical history were collected from hospital records. Areal bone mineral density (aBMD) for the lumbar spine (L1-L4), femoral neck and whole body as well as volumetric BMD (vBMD) for the lumbar spine (L2-L4) were measured with dual-energy X-ray absorptiometry (DXA). RESULTS: Mean age was 34 years (range 21-59 years). All patients had 1-4 autoimmune endocrinopathies, the most common being adrenocortical failure (20 patients) and hypoparathyroidism (18 patients). Osteopaenia or osteoporosis was present in 28%. The median (range) aBMD Z-scores were for the lumbar spine -0.3 (-2.3 to +3.3) and for the femoral neck, -0.1 (-2.2 to +2.0). The BMD Z-scores tended to be higher in patients with hypoparathyroidism than in patients with normal parathyroid function (at the lumbar spine +0.4 vs.-1.2, P = 0.016, and at the femoral neck +0.3 vs.-0.4, P = 0.090). Adrenocortical failure had a negative impact on BMD. Six patients had had low-impact fractures and three were diagnosed with compression fractures. CONCLUSIONS: Despite the complex endocrine problems, the overall prevalence of symptomatic osteoporosis is low in adults treated for APECED. Osteopaenia is frequently observed and warrants follow-up. Treated hypoparathyroidism may have a positive, and adrenocortical failure a negative, impact on bone health.

Skeletal phenotype in patients with Shwachman-Diamond syndrome and mutations in SBDS.

Pancreatic exocrine and bone marrow dysfunctions are considered to be universal features of Shwachman-Diamond syndrome (SDS) whereas the associated skeletal dysplasia is variable and not consistently observed. The genetic defect in SDS has recently been identified; causative mutations have been shown in the SBDS gene. The aims of this study were to characterize the nature, frequency, and age-related changes of radiographic skeletal abnormalities in patients with SBDS mutations and to assess genotype-phenotype correlation. Fifteen patients (mean age 9.7 years) with a clinical diagnosis of SDS and documented SBDS gene mutations were included. Review of their skeletal radiographs showed abnormalities in all patients. The skeletal changes were variable, even in patients with identical genotypes. The typical features were (1) delayed appearance of secondary ossification centers, (2) variable widening and irregularity of the metaphyses in early childhood, followed by progressive thickening and irregularity of the growth plates, and (3) generalized osteopenia. There was a tendency towards normalization of the epiphyseal maturation defect and progression of the metaphyseal changes with age. The results suggest that the characteristic skeletal changes are present in all patients with SDS and SBDS mutations, but their severity and localization varies with age. No phenotype-genotype correlation was observed.

Does dietary protein intake correlate with markers suggestive of early diabetic nephropathy in children and adolescents with Type 1 diabetes mellitus?

AIMS: To examine the relationship between dietary protein intake and possible early markers of diabetic nephropathy (creatinine clearance (CrCI), kidney volume and albumin excretion rate (AER)). METHODS: One hundred and forty-five subjects with diabetes for 5-10 years, divided into three pubertal groups, participated. Kidney volume was measured by ultrasound, and serum creatinine and HbA1c were assayed. Two or three 24-h urine collections were obtained for albumin, creatinine and urea excretion rates. Dietary protein intake was estimated from urinary urea nitrogen excretion rate. Glomerular filtration rate was estimated by creatinine clearance. RESULTS: Mean protein intake was 1.22 +/- 0.48 g x kg(-1) x day(-1) Protein intake was significantly higher in males than females (P < 0.0001) and highest in prepubertal compared to mid-pubertal and post-pubertal subjects (P < 0.001). In multiple regression analysis, protein intake was positively associated with CrCl (P < 0.0001), and male sex (P < 0.0001) and negatively associated with body surface area (P = 0.0013) and age (P = 0.01). Kidney volume and AER were not related to dietary protein intake. CONCLUSIONS: This cross-sectional study failed to show a significant relationship between dietary protein intake and markers of early nephropathy, other than CrCl. However, a longitudinal, prospective study is required to definitively assess the role of protein intake in the evolution of diabetic nephropathy.

Intensive diabetes management decreases Na-Li countertransport in young subjects with type 1 diabetes and enlarged kidneys.

In type 1 diabetes, increases in sodium-lithium countertransport (Na-Li CT), kidney volume (KV), and albumin excretion rate (AER) may precede the development of persistent microalbuminuria. Limited data exist on reversibility of these factors early in the evolution of diabetic nephropathy. A crossover design was used to study the separate effects of enalapril and intensive diabetes management (IDM) on Na-Li CT, KV and AER in 17 children and adolescents with type 1 diabetes (5-10 years duration) with large kidneys (>275 ml/1. 73 m(2)) and predominantly normoalbuminuria. Subjects were randomized to receive 3 months of either enalapril (0.25 mg/kg/day) or IDM, a 3-month washout, followed by the alternate treatment for 3 months. During IDM, HbA1c decreased 2.5% (pre 9.5+/-0.3% (mean+/-SE), post 7.0+/-0.1%, p<0.0001), but was unchanged while on enalapril (pre 8.8+/-0.3%, post 8.5+/-0.3%, p=0.1). A significant decrease in Na-Li CT was seen with IDM (pre 0.43+/-0.05, post 0.36+/-0.04 mmol/l RBC/h, p=0.006) but not angiotensin converting enzyme inhibition (ACE-i) (pre 0.39+/-0.04, post 0.38+/-0.04 mmol/RBC/h, p=0.4). Neither ACE-i nor IDM affected KV or AER. It is concerning that kidney enlargement does not appear reversible at this early stage in the pathogenesis of diabetic nephropathy, although our conclusions are limited by the short duration of intervention and small sample size. The reduction in Na-Li CT with IDM suggests this may be a potentially modifiable risk factor for diabetic nephropathy.

Carotid artery distensibility and cardiac function in adolescents with type 1 diabetes.

OBJECTIVE: To determine the presence and correlates of early heart and blood vessel dysfunction in adolescents with type 1 diabetes mellitus (DM) of relatively short duration. STUDY DESIGN: A total of 33 patients with DM (20 male, mean age 15.8 +/- 1.3 years, mean DM duration 9.3 +/- 3.9 years) and 16 healthy subjects in a nondiabetic control group (7 male, mean age 17.4 +/- 1.7 years) underwent (1) ultrasonography of the right carotid artery to assess distensibility, compliance, and intimal-medial thickness (IMT), (2) echocardiographic assessment of systolic and diastolic ventricular function, (3) lipid profile and hemoglobin A(1c), and (4) overnight timed urine collections for albumin excretion rate. RESULTS: Ultrasonography showed significantly lower carotid artery distensibility in the DM group (38.5 +/- 8.2 x 10(-3) vs 46.5 +/- 11.7 x 10(-3)/kPa, P =.01) but no difference in compliance (14.0 +/- 3.4 x 10(-7) vs 15.8 +/- 2.9 x 10(-7)m(2)/kPa, P =.08) or IMT (0.061 +/- 0.013 vs 0.060 +/- 0.014 cm, P =.77). Left ventricular (LV) end-diastolic diameter, LV posterior wall thickness, end-systolic wall stress, shortening fraction, ejection fraction, LV mass, and diastolic function were similar in both groups. Total cholesterol, low density lipoprotein, high density lipoprotein, triglycerides, and blood pressure were also similar. The median albumin excretion rate was 4.8 microg/min in the DM group (range 1.1 to 19.2) and 3.0 microg/min in the control group (range 1.4 to 5.8) (P =.03). Hemoglobin A(1c) correlated inversely with both distensibility (r = -.43, P =.02) and compliance (r = -.39, P =.032). CONCLUSIONS: This study indicates that early changes in macrovascular function, namely lower carotid artery distensibility, may precede abnormalities in cardiac function or in arterial IMT in adolescents with short duration type 1 DM. It also supports a relationship between hyperglycemia and carotid artery dysfunction.

Cyclophosphamide and water retention: mechanism revisited.

We describe an 8 year-old girl with established diabetes insipidus who developed cyclophosphamide-associated antidiuresis. The patient had received cyclophosphamide as part of a high-dose chemotherapy regimen for recurrent suprasellar dysgerminoma prior to autologous bone marrow transplantation. Urinary output decreased and specific gravity increased shortly after a 1 hour i.v. infusion of 50 mg/kg cyclophosphamide and the effect lasted some 5 hours. No other drug could be implicated. This response, occurring in a patient with no ability to secrete vasopressin, suggests a direct tubular effect of one or more cyclophosphamide metabolites. Administering i.v. cyclophosphamide requires careful monitoring of fluid balance in order to avoid water intoxication. Further research is warranted both into the mechanism of this effect and the metabolite responsible for it.

Intensive diabetes management in adolescents with type 1 diabetes: the importance of intensive follow-up.

Minimal information exists on the education and follow-up required to successfully initiate intensive diabetes management (IDM) in adolescents with type 1 diabetes. We performed a retrospective analysis of HbA1c 3 and 15 months after initiation of IDM in two cohorts: (1) 17 patients who received individualised education in IDM and intensive early follow-up, and (2) 11 patients who participated in group education for initiation of IDM with standard follow-up. Entry HbA1c was higher in the individualised education patients (9.5 +/- 0.3% [mean +/- SE] versus 8.2 +/- 0.4%, p = 0.02). After 3 months of IDM, HbA1c improved in both cohorts reaching similar levels (individualised: 7.0 +/- 0.1%, p < 0.0001 vs entry; group: 7.3 +/- 0.2%, p = 0.05). During the following year, with routine follow-up for both cohorts, HbA1c levels rose approximately 1% as patients reverted to a multiple daily injection regimen. Irrespective of the educational approach, we believe maintenance of IDM and optimal HbA1c requires long-term intensive follow-up.

A trial of growth hormone therapy in well-controlled hypophosphataemic rickets.

OBJECTIVE: Conventional therapy of hypophosphataemic rickets (HR) with oral phosphate and calcitriol does not always result in normal linear growth. Recombinant human growth hormone (rhGH) offers theoretical advantages as an adjunctive therapy. We aimed to determine the effects of adjunctive rhGH therapy in children with well-controlled HR. PATIENTS: In this report, 5 prepubertal children (aged 3.5-10.9 years) with well-controlled HR on conventional therapy were given adjunctive standard dose rhGH therapy for one year. DESIGN AND MEASUREMENTS: Height, growth velocity, metabolic markers of calcium and phosphate metabolism, body composition, bone mineral density, wrist and knee X-rays, and renal sonography were assessed at regular intervals. Height and growth velocities were also calculated 12 months after ceasing rhGH therapy. RESULTS: After 12 months therapy with rhGH, no significant biochemical or radiological benefits were observed. A significant increase in height SD score was observed (P = 0.023), but this was not associated with any increase in the growth velocity SD score and appears to have been due to catch-up growth caused by conventional therapy alone. When rhGH therapy was ceased, no significant decreases in mean height SD or growth velocity SD scores were observed. CONCLUSIONS: In well-controlled hypophosphataemic rickets patients receiving conventional therapy, adjunctive therapy with standard dose rhGH offers no benefits in linear growth or rachitic disease markers.

Contribution of growth hormone and IGF-I to early diabetic nephropathy in type 1 diabetes.

In children and adolescents with type 1 diabetes, we have reported an association between duration of puberty and the prevalence of nephromegaly and microalbuminuria (MA), which are early markers of diabetic nephropathy. Growth hormone (GH), IGF-I, testosterone, and prorenin are potential mediators of this effect. This study examined the relationship of these hormonal factors to kidney volume (KV) and MA in 155 subjects (78 males, age 13.2 +/- 3.5 years [mean +/- SD]) with similar diabetes duration (6.83 +/- 1.6 years) but varying pubertal experience (0-10 years). KV (by ultrasound), plasma IGF-I, testosterone, prorenin, and NaLi countertransport, and urinary albumin, urinary GH, and urinary IGF-I from three 24-h collections were measured. Multiple regression analysis showed that BSA (P < 0.0001) and urinary IGF-I (P = 0.001) were significantly associated with KV. MA subjects (albumin excretion rate 15-200 microg/min) had higher urinary IGF-I (P = 0.005) and urinary GH (P = 0.05) compared with normoalbuminuric subjects. Only 9% of the variance in urinary IGF-I could be attributed to plasma IGF-I (r = 0.30, P < 0.0001). Testosterone and prorenin were not associated with MA, but they were associated with KV in univariate analyses. The strong association of urinary IGF-I with KV, a marker for glomerular hypertrophy, and of both urinary IGF-I and urinary GH with MA suggests a role for these growth factors in the development of human diabetic nephropathy. Together, these data support animal studies that have shown that renal GH and IGF-I may contribute significantly to the pathogenesis of early diabetic nephropathy.

Frequency and characteristics of lingual thyroid not detected by screening.

Four patients with lingual thyroid glands presenting beyond the neonatal period have been evaluated at the Hospital for Sick Children, Toronto since the advent of neonatal TSH screening. All were female, clinically euthyroid at diagnosis and presented with symptoms of a lingual mass. We estimate that 1.6% of lingual thyroids are missed by this TSH based thyroid screening program and approximately 1/600,000 live births present in childhood or adolescence with a lingual thyroid. Physicians should still include lingual thyroid in the differential diagnosis of a mass at the base of the tongue.

Ambulatory blood pressure monitoring in insulin-dependent diabetes mellitus adolescents with and without microalbuminuria.

The aim of our study was to compare ambulatory blood pressure monitoring (ABPM) measures (mean systolic/diastolic blood pressure, diurnal rhythm, and pressure burden) in matched normo- and microalbuminuric (IDDM) adolescents and healthy controls. Twenty-four hour monitoring was undertaken in 39 normotensive (normal clinic blood pressure measurements) IDDM adolescents (22 normo- and 17 microalbuminuric subjects) and 23 controls. Subjects were matched for age, bodymass index, gender, and IDDM duration. Microalbuminuria was diagnosed on the basis of a urinary albumin excretion rate greater than 15 but less than 200 micrograms/min in two of the three 24-h urine collections. The microalbuminuric patients differed from the normoalbuminuric subjects and controls in having higher mean 24-h and overnight systolic pressure, loss of systolic diurnal rhythm and increased systolic and diastolic pressure burden. There were no differences between the three groups in diastolic blood pressure. The normoalbuminuric group differed from the controls only with respect to an increased systolic pressure burden. Microalbuminuric IDDM adolescents show similar, albeit milder changes in ABPM, to those reported in adults with microalbuminuria. We postulate that these milder changes represent an earlier phase to that observed in the adult population and that taken together, the adolescent and adult data suggests a specific order in the development of ABPM changes in diabetic subjects.

Urinary growth hormone: a screening test for growth hormone sufficiency.

OBJECTIVES: The majority of short statured children referred for serum GH testing prove to be GH sufficient. The purpose of our study was to evaluate urinary growth hormone (uGH) as a screening test for GH sufficiency. PATIENTS: We studied (i) short statured children previously diagnosed as GH sufficient (n = 44) or GH deficient (n = 41) (peak serum GH > or = 8 micrograms/l or < 8 micrograms/l, respectively); (ii) short children undergoing serum GH stimulation tests (n = 23, test group); (iii) normal statured children (n = 45, control group). DESIGN: Three separate overnight urine collections were obtained in all groups. GH injections in GH deficient subjects were discontinued 4 days prior to urine collection. MEASUREMENTS: uGH concentrations were measured using a chemiluminescence immunoassay. Overnight uGH was expressed in several ways (overnight excretion and overnight excretion corrected for body surface area, time and creatinine). Receiver operator curves (ROC) were constructed from the data obtained in the GH sufficient and deficient subjects. Sensitivity and specificity were then determined for various urinary cut-offs. These cutoffs were validated in turn in the test group by comparison of the predicted with the observed GH status. RESULTS: The GH deficient group had the lowest GH output with respect to overnight uGH, overnight uGH/m2, overnight uGH/h and overnight uGH/creatinine when compared with the GH sufficient and control groups (P = 0.0001). Overnight uGH/m2 data gave the greatest area under the ROC curve. At 100% specificity (no GH deficient subjects), it had the highest sensitivity, 63.6% (49.2-78.0% CI) at a cut-off of 2.3 ng/m2 (63.6% of GH sufficient subjects had uGH levels > 2.3 ng/m2). When this and other cut-offs were applied to the test group, we found consistency between the observed and predicted numbers of GH sufficient and deficient subjects. CONCLUSIONS: We conclude that urinary GH is a useful test for the diagnosis of GH sufficiency as defined by serum criteria and can be used to reduce significantly the number of serum stimulation tests.

Effect of puberty on markers of glomerular hypertrophy and hypertension in IDDM.

Epidemiological data implicate puberty as a factor in the initiation of diabetic nephropathy. However, the mechanism remains unclear. We hypothesized that puberty would result in an increase in glomerular hypertrophy and hypertension; these two early concomitant events are seen as pivotal to the pathophysiology of diabetic nephropathy. We studied the effect of pubertal duration on three surrogate markers of glomerular hypertrophy/hypertension: kidney volume (KV), microalbuminuria (MA), and Na-Li countertransport (CT). We recruited 177 subjects (87 female and 90 male; aged 6.2-22.1 years) with IDDM of 5 to 10 years' duration (6.8 +/- 1.6 years) into three groups with different pubertal duration: prepubertal since IDDM diagnosis; prepubertal at diagnosis, now pubertal; or early puberty at diagnosis, now postpubertal. KV was measured by ultrasound and corrected for body surface area; MA was defined as urinary albumin excretion of 15-200 micrograms/min in two of three 24-h samples, and Na-Li CT was measured in erythrocytes. As pubertal duration increased, there was a disproportionate increase in mean KV (prepubertal, 247 +/- 6 [SE] ml/1.73 m2; pubertal, 282 +/- 7/1.73 m2; postpubertal, 295 +/- 7/1.73 m2, P = 0.001), prevalence of nephromegaly (KV > 300 ml/1.73 m2) (14, 31, and 45%, respectively, P = 0.001), and prevalence of MA (0, 9.7, and 20.5%, respectively, P = 0.003). Subjects with KV > 300 ml/1.73 m2 were eight times more likely to have MA than those with KV < 300 (odds ratio 8.1, 95% confidence interval 2.4-27.4, P = 0.0001). There was no effect of pubertal duration on Na-Li CT. Multiple regression with KV as the dependent variable found an association with pubertal duration, MA, Na-Li CT, and current HbA1c (P < 0.0001). Our findings indicate that pubertal duration is an important determinant of both KV and MA and suggest that nephromegaly precedes microalbuminuria. We postulate that these effects are attributable to the influence of the pubertal milieu on glomerular hypertrophy/hypertension.

Plasma prorenin as an early marker of nephropathy in diabetic (IDDM) adolescents.

We studied a group of 50 adolescents, average age 16 years, with diagnosed IDDM present for about seven years. Twenty-five had microalbuminuria (MA) averaging 111.0 +/- 34.0 (SEM) micrograms/min albumin excretion rate versus 6.7 +/- 7.4 micrograms/min in the 25 without MA. In other respects, such as sex ratio, age, body mass index, duration of IDDM, hemoglobin A1c, and normotensive systolic, diastolic and mean blood pressures (BP), these subgroups were closely matched. We compared them with a control group of 39 normotensive adolescents, of whom 18 were carefully matched siblings of the IDDM subjects with MA and 21 were similarly matched siblings of the IDDM non-MA subjects. Plasma renin concentration was determined by a direct radioimmunoassay method (Sanofi-Pasteur) and found to be virtually the same in the control and IDDM adolescents as a whole. There was also no real difference between the MA and non-MA subgroups. In contrast, plasma prorenin was significantly higher in the combined IDDM group (197.5 +/- 9.3 vs. control, 134.0 +/- 7.9 pg/ml, P < 0.0001). It was also higher in the MA subgroup than in the non-MA subgroup (226.4 +/- 13.6 vs. 168.5 +/- 10.1 pg/ml, P < 0.001). Interestingly, the 18 control siblings matching the MA subgroup had higher plasma prorenin than the 21 control siblings matching the non-MA subgroup (P < 0.001), suggesting a familial predisposition that precedes detectable diabetes and nephropathy. Our findings confirm and extend reports by other workers that elevated plasma prorenin is associated with incipient nephropathy, manifested by MA. The exclusive renal origin of this prorenin, its role in plasma, and the mechanism responsible for its elevation in IDDM with MA, are yet to be demonstrated, as is the general applicability of these findings to different populations of diabetics, with a higher incidence and severity of complications.

Factors affecting and patterns of residual insulin secretion during the first year of type 1 (insulin-dependent) diabetes mellitus in children.

We measured serum C-peptide, glucose, pH, islet antibodies and insulin antibody binding at diagnosis in 84 children with Type 1 (insulin-dependent) diabetes. In a subgroup of 33 children, residual insulin secretion (basal and peak C-peptide response to Sustacal), insulin antibody binding and HbA1c were measured at 10 days, 1, 3, 6 and 12 months. At presentation C-peptide correlated positively with age at onset and negatively with the blood glucose concentration. Median C-peptide concentration at diagnosis was low, rose significantly (p less than 0.05) at 10 days, reached a maximum at 1-3 months and declined gradually to 1 year. C-peptide concentration both at diagnosis and at 10 days correlated with that at 3 and 6 months. Of the factors investigated, only age (p less than 0.005) and sex (higher in females, p less than 0.01) were found to have a significant influence on basal/peak C-peptide levels throughout the first year. In particular there was no relationship between C-peptide, HbA1c and insulin dose during this period. A peak C-peptide response at 3-6 months greater than/less than 0.32 nmol/l was used to divide the group into two: 16 had a peak response less than 0.32 nmol/l (low secretors) while in 17, the peak C-peptide was greater than 0.32 nmol/l (high secretors). While the low secretors had significantly (p less than 0.05) lower C-peptide levels during the first year, there were no differences between low and high secretors in HbA1c or insulin dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Vitamin D status in hospitalized black children under 2 years of age.

The apparent decline over the last decade of vitamin D deficiency rickets among black infants in South Africa has suggested a significant improvement in their vitamin D status. Levels of serum 25-hydroxy-vitamin D, calcium, phosphorus and alkaline phosphatase, together with a radiograph of the left wrist, were obtained in 114 hospitalized black infants under the age of 2 years in order to establish the frequency of infants with or at risk of vitamin D deficiency. Mean 25-hydroxyvitamin D levels were found to be in the low normal range and showed no correlation with either age or season. Vitamin D stores were depleted in 7% and relatively deficient in 20,7% with suggestive radiological features of rickets in only 2 patients. The high prevalence of malnutrition and infection made a biochemical assessment of rickets impossible. The significance of these suboptimal vitamin D levels is uncertain, but the available literature would suggest that these infants are at increased risk of developing vitamin D deficiency rickets.