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PubMed1994

Angiotensin-converting enzyme inhibition partially prevents diabetic organomegaly.

The present study was conducted to evaluate whether captopril prevents the organomegaly and accumulation of matrix proteins that normally accompanies the diabetic state. The following groups of rats were studied: normal rats, normal rats treated with captopril (30 mg/kg/d orally), streptozotocin diabetic rats, and diabetic rats treated with captopril. All rats were killed at 10 weeks for histologic and morphometric evaluation of tissues. Compared with the normal rats, the diabetic rats demonstrated significant hepatomegaly, nephromegaly, and cardiomegaly, and the increase in organ size was directly related to increasing levels of protein glycosylation. The development of organomegaly was partially prevented by captopril. We determined by morphometry that the hepatomegaly seen in the diabetic rats was due to an increase in cell size and number, while the nephromegaly seen in the diabetic rats was due to an increase in tubular and glomerular cell size and is associated with glomerular hypertrophy. Captopril prevented the development of hepatic and renal cell hypertrophy and glomerular hypertrophy. These effects of captopril were not associated with detectable changes in body weight or levels of glucose, protein glycosylation, glycosuria, or renal histologic changes secondary to glycosuria. The diabetic rats demonstrated significant glomerular mesangial matrix expansion, and captopril treatment partially prevented that expansion. In conclusion, captopril prevents, in part, the development of organomegaly in diabetic rats, and this effect is due mainly to the prevention of the development of cellular hypertrophy. The present findings are most consistent with a direct effect of captopril on cell metabolism during diabetes mellitus.

Analysis of Variance↗
PubMed1989

Two case studies from a family with primary Fanconi syndrome.

We report two cases from a family with primary Fanconi syndrome. A 39-year-old white woman with a history of frequent bone fractures developed hypophosphatemia, hypouricemia, hypokalemia, metabolic acidosis, and renal glycosuria. Her 15-year-old son had renal glycosuria without metabolic acidosis. Both had mildly to moderately impaired renal function. Determination of amino acids in 24-hour urine specimens confirmed the generalized nature of aminoaciduria. Acid-loading, bicarbonate-loading, and phosphate-loading tests revealed that the mother had proximal (type II) renal tubular acidosis and excessive renal loss of phosphate for her level of renal function. These tests for the son were normal or within normal limits of his renal function. Known causes of Fanconi syndrome, such as cystinosis and Wilson's disease, were excluded by slit-lamp eye examination and leukocyte cystine level determination. One unexpected finding in the son was the preseNce of nephrocalcinosis on x-rays; a percutaneous needle biopsy of the kidney showed tubular atrophy, interstitial fibrosis, and calcium oxalate crystal deposits. The two cases presented here represent a familial variety of the primary Fanconi syndrome, a rare entity with a limited number of cases reported in the literature.

Adolescent↗
PubMed1998

Protective role of Anacardium occidentale extract against streptozotocin-induced diabetes in rats.

The protective effect of Anacardium occidentale aqueous extract against streptozotocin-induced diabetes was evaluated in rats. The rats were treated with 175 mg/kg of the extract per os, twice daily; beginning 2 days before streptozotocin (STZ) injection. A total of 3 days after STZ administration, there was a 48% increase in blood glucose level in pretreated rats, compared with a 208% increase in diabetic control rats treated with STZ alone. Furthermore, these pretreated animals presented no glycosuria, a normal weight gain and a non significant increase in food and fluid intake at the end of the treatment compared with the normal control. Diabetic control animals showed a positive glycosuria, body weight loss, a real polyphagia and polydypsia. These results indicate the protective role of Anacardium occidentale extract against the diabetogenic action of STZ.

Animals↗
PubMed2002

Bilateral symmetric polyarthralgia revealing Fanconi's syndrome.

We report the case of a 45-year-old woman who presented with a six-year history of diffuse polyarthralgia responsible for major disability. She reported bilateral symmetric arthralgia in nearly every joint, as well as back pain. Muscle wasting predominating in the roots of the limbs was found. Laboratory tests showed hypocalcemia, severe hypophosphatemia, hypokalemia, alkaline phosphatase elevation, aminoaciduria, and hyperphosphaturia, with no glycosuria. Radiographs disclosed osteolysis of the pubic symphysis, multiple pelvic fractures, vertebral compression fractures, and diffuse demineralization. A bone scan visualized symmetric foci of hyperactivity in nearly all joints and fracture sites. Dramatic improvements in clinical and radiographic abnormalities were noted after six months of treatment with phosphate and calcitriol. This is a case of incomplete Fanconi syndrome, with no glycosuria. The clinical presentation of Fanconi syndrome can be misleading. Fanconi syndrome should be borne in mind as a possible cause of polyarthralgia to avoid diagnostic delay, which in our patient led to a picture of pseudomyopathy with multiple fractures.

Arthralgia↗
PubMedDate not supplied

Pregnancy complications in natural family planning users.

A multicenter cohort study was designed to assess pregnancy outcome among natural family planning (NFP) users, and provide the opportunity to address complications in NFP users by planning status and by timing of conception with respect to day of ovulation. There were 877 singleton births in this sample. Complications evaluated were abnormal vaginal bleeding, urinary tract infection, vaginal infection, hypertension of pregnancy, proteinuria, glycosuria, and anemia. There was no significant difference in the mean age, number of prenatal visits or birth weight among optimally and non-optimally timed pregnancies or for planned and unplanned pregnancies. There were higher incidences of "parity 2 or more" and current smokers in the non-optimally timed pregnancies and lower incidences of prior pregnancy loss and "currently employed" in the non-optimally timed pregnancies. There was little difference in pregnancy complications with respect to pregnancy timing, with the exception of a significant increased risk of vaginal bleeding late in pregnancy among non-optimally timed conceptions (11.5%) compared to optimally timed pregnancies (5.2%, RR = 2.2, 95% CI 1.3-3.7). More differences were observed in pregnancy complication rates by planning status. Unplanned pregnancies were associated with significantly more late pregnancy bleeding, vaginal infections, proteinuria, glycosuria and medication use than planned pregnancies. Unplanned pregnancies had lower incidences of maternal anemia. Complications of pregnancy were low in this NFP population, irrespective of planned versus unplanned status. Women with planned pregnancies had even fewer complications during pregnancy than women with unplanned conceptions, suggesting that women using NFP to plan their reproduction may be at particularly low risk.

Cohort Studies↗
PubMed1991

Impact of environmental stress on the expression of insulin-dependent diabetes mellitus.

To investigate the influence of environmental factors on inherited tendencies, the impact of chronic environmental stress on the expression of a genetically determined autoimmune disease was explored in the bio-breeding (BB) rat, which is an animal model for human autoimmune insulin-dependent diabetes mellitus. Animals assigned at random to the experimental group received a triad of stressors designed to model chronic moderate stress over a 14-week period. Animals from 25 to 130 days of age were weighed and tested for glycosuria twice weekly. Weekly blood sampling was performed on all animals. Diabetes was diagnosed on the basis of weight loss, 2+ glycosuria, and blood glucose levels of 250+ mg/dl. We found that in the BB rat chronic stress significantly increased the incidence of the phenotypic expression of the gene for Type I diabetes. Eighty percent of the male stress and 70% of the female stress animals developed diabetes, compared with 50% in both control groups. Stressed males developed manifest diabetes at the same time as their matched controls, whereas stressed females had significantly delayed onset in relation to controls.

Animals↗
PubMed1982

Diabetic nephropathy in the uninephrectomized dog: microscopic lesions after one year.

Carefully age-matched, purebred male beagle dogs that underwent uninephrectomy one month after they were made diabetic with alloxan were used to establish a model of rapidly developing diabetic nephropathy in a large animal. The diabetic animals, all requiring insulin, were divided into two groups: one group with control by insulin injections permitting elevated fasting and postprandial serum glucose values and substantial glycosuria; the other with better control and with near-normal serum glucose levels and less glycosuria. By 1 year of diabetes both diabetic groups had renal lesions different from the uninephrectomized control animals but differing only slightly from one another. With light microscopy, diabetic dogs had increased mesangial thickening. With electron microscopic morphometry, glomeruli of diabetic subjects demonstrated increased fractional volumes of the total mesangium and of its cellular and matrix components and increased width of the GBM. These quantitative measures of diabetic nephropathy in the dog within 1 year of onset of the disease describe a model potentially useful in evaluating the efficacy of improved diabetic control in preventing or ameliorating diabetic nephropathy.

Animals↗
PubMed2002

Dietary patterns and risk factors for type 2 diabetes mellitus in Fijian, Japanese and Vietnamese populations.

Diabetes mellitus is now a serious and increasing problem in Asian countries, where dietary patterns have shifted toward Westernized foods and people are becoming more sedentary. In order to elucidate the relationship of dietary habits to the development of diabetic risk factors, the dietary patterns of 200 Fijian, 171 Japanese and 181 Vietnamese women of 30-39 years of age were investigated using 3 day-24 h recall or dietary records. Anthropometric measurements and glycosuria tests were also conducted. The dietary trends of Fijians and Japanese have changed drastically in the past 50 years, while Vietnamese have been minimally influenced by Western dietary habits. The mean 24 h dietary intake showed that Fijians had the highest energy intake. Energy intake from fat was only 13% for Vietnamese, but over 30% for Japanese and Fijians. Percentage of body fat was higher in Vietnamese than in Japanese, though there were no significant differences in body mass index (BMI). In the overweight and obese women, Vietnamese had higher abdominal obesity than Japanese. The prevalence of obesity (BMI > or = 30 kg/m2) was 63.0% for Fijians, 1.8% for Japanese and 1.1% for Vietnamese. Glycosuria testing yielded the most positive cases among Fijians. Dietary transition and dietary excess appear to be potential risk factors for diabetes in Fijian women.

Adipose Tissue↗
PubMed2001

Prevalence of undiagnosed diabetes mellitus in male erectile dysfunction.

OBJECTIVE: To determine the prevalence of previously undiagnosed diabetes mellitus (DM) in men presenting with erectile dysfunction (ED), using fasting blood glucose (FBG) compared with urinary dipstick testing for glycosuria. PATIENTS AND METHODS: A prospective prevalence study was carried out in an andrology outpatient clinic of a urology department in a district general hospital serving a mixed urban and rural population. In all, 129 consecutive men presenting with ED underwent FBG and urinary dipstick testing to detect undiagnosed DM in those presenting with ED. RESULTS: The prevalence of known DM was 17% and the that of undiagnosed DM 4.7% of the 107 remaining men; an abnormal fasting glucose level was found in a further 12%. The sensitivity of urine dipstick test for diagnosing DM was 20%. CONCLUSIONS: The prevalence of undiagnosed DM is higher in men with ED than in the general population. ED is a marker symptom for DM and DM should be actively sought in men presenting with ED. Urinary dipstick testing for glycosuria, if used as a screening test, will miss the diagnosis in 80% of these men. FBG testing should be undertaken to reliably diagnose DM in men presenting with ED.

Adult↗
PubMedDate not supplied

Single local instillation of Staphylococcus aureus peptidoglycan prevents diabetes-induced impaired wound healing.

Diabetes-induced impaired wound healing is characterized by inhibition of the inflammatory response to wounding, macrophage infiltration, angiogenesis, fibroplasia, reparative collagen accumulation, and wound breaking strength. Because all of these processes are accelerated in normal rats by a single local application at operation of Staphylococcus aureus peptidoglycan, we hypothesized that S. aureus peptidoglycan would prevent diabetes-induced impaired wound healing, despite persistent, untreated hyperglycemia, polydipsia, glycosuria, and polyuria. Sprague- Dawley male rats were divided into two groups. One group received an intraperitoneal injection of streptozotocin (65 mg/kg) in citrate solution; the other group received an intraperitoneal injection of an equivalent volume of citrate solution. Seventeen days after the injections, the diabetic and control rats received aseptically two 5.5-cm paravertebral incisions and subcutaneous implantation of six polyvinyl alcohol sponges, three on each side. On one side, each sponge contained 0.5 mg S. aureus peptidoglycan in 50 microliter saline solution, and the incision was inoculated along its length with 4.7 mg S. aureus peptidoglycan in 157 microliter saline solution (860 microgram/S. aureus peptidoglycan/cm incision); on the other side, the same respective volumes of saline were used. During the preoperative and postoperative periods, diabetic rats lost a small amount of weight (2%), were hyperglycemic (363 +/- 10 mg/100 ml blood), polydipsic, glycosuric, and polyuric, whereas the controls gained weight (25%) and were normoglycemic (104 +/- 5 mg/100 ml blood); these differences were significantly different (p <.001 in each case). In controls, S. aureus peptidoglycan inoculation increased wound breaking strength (by a factor of 2.0) and hydroxyproline content (by a factor of 1.4; p <.001 in each case); in diabetics, there were significant decreases in wound breaking strength (by a factor of 1.7) and hydroxyproline content (by a factor of 1.3) of saline solution-inoculated incisions and sponges compared with the wound breaking strength and hydroxyproline content of saline solution-inoculated incisions and sponges in controls (p <.02 and p <.001, respectively). These decreases were completely prevented when the incisions and polyvinyl alcohol sponges had been inoculated at operation with S. aureus peptidoglycan; S. aureus peptidoglycan inoculation in the diabetic rats increased wound breaking strength by a factor of 2.2 and sponge reparative tissue hydroxyproline by a factor of 1.6 (p <.001 in each case). Thus, diabetes-induced impaired wound healing was prevented completely by a single local instillation at operation of S. aureus peptidoglycan, despite persistent, untreated hyperglycemia, polydipsia, polyuria, and glycosuria.

Animals↗
PubMed2002

A three-day insulin-induced normoglycemia improves carbohydrate oxidation in type 2 diabetic subjects.

Two months of a better glycemic control improve carbohydrate oxidation in type 2 diabetes. However, this benefit is uncertain for a shorter duration. We tested the effect of 3 days of normoglycemia induced by an insulin infusion. Ten type 2 diabetic subjects (body mass index [BMI], 30.0 +/- 1.1; glycosylated hemoglobin [HbA(1C)], 10.1 +/- 0.5) were studied twice, before and after normal glucose levels were maintained by a 72-hour intravenous insulin infusion. Indirect calorimetry was performed 1 hour before (basal) and during the 3 hours after (postprandial) the ingestion of a standard meal (carbohydrates, 72 g; fat, 21 g; protein, 32 g), at noon. Carbohydrate storage was calculated as ingested carbohydrate - (postprandial glycosuria + suprabasal postprandial carbohydrate oxidation). After normoglycemia, glucose and triglyceride levels were decreased (basal glucose, 13.8 +/- 1.1 mmol/L to 8.8 +/- 0.5; postprandial, 14.9 +/- 0.9 to 11.0 +/- 0.5; basal triglycerides, 2.2 +/- 0.1 mmol/L to 1.6 +/- 0.2; postprandial, 2.7 +/- 0.2 to 1.9 +/- 0.2; all P <.01), C peptides were unchanged. Glycosuria (before, 0.30 mg/kg/min) was abolished after normoglycemia. Basal carbohydrate, lipid, protein oxidation, and energy production rates were unchanged. Postprandial carbohydrate oxidation was increased after normoglycemia (before, 1.33 +/- 0.38 mg/kg/min; after, 1.77 +/- 0.42; P <.05). Lipid oxidation and plasma free fatty acids (FFA) tended to be more suppressed by the meal after normoglycemia (not significant [NS]). Carbohydrate storage (before, 67,5 +/- 4.6 g; after, 65.7 +/- 3.6; NS) and diet-induced thermogenesis did not change after normoglycemia. Short-term insulin-induced normoglycemia improves the postprandial oxidation of carbohydrates, but not their storage.

Blood Glucose↗
PubMed1986

Magnesium status in children with insulin-dependent diabetes mellitus.

We assessed the magnesium status in 67 children with insulin-dependent diabetes mellitus (IDDM) in various degrees of diabetic control and its changes during the evolution of the disease. This was done by measuring fasting serum magnesium and 24-hr urinary magnesium clearances when patients were first studied, as well as subsequently on follow-up. In 23 of these patients the retention of intramuscular magnesium was also assessed in relation to the degree of diabetic control and the duration of the illness. The mean +/- SD serum magnesium levels were significantly lower in diabetic children as compared to nondiabetic controls (1.91 +/- 0.22 vs 2.12 +/- 0.26 mg/dl, p less than 0.001). Serum magnesium in diabetic children correlated with glycosylated hemoglobins (r = -0.358, p less than 0.001), but not with 24-hr glycosuria (r = -0.296). On follow-up of patients, serum magnesium significantly increased when IDDM control improved and decreased when the control worsened. Diabetic patients had increased urinary magnesium clearances compared to nondiabetic subjects (5.26 +/- 3.58 vs 3.60 +/- 1.36 cc/min, p less than 0.05). All but five of the 23 patients given the magnesium load retained more than 40% of the dose, with a mean +/- SD retention of 58.7 +/- 5.1%. There was no correlation between the amount of retained magnesium and the duration of the illness, degree of diabetic control, amount of glycosuria, magnesuria, magnesemia, glycosylated hemoglobins, or serum lipids. The data confirm that lower than control serum magnesium levels occur frequently among children with poorly controlled IDDM. Moreover, there might be magnesium deficiency in IDDM, as indicated by the high retention of magnesium when given intramuscularly. The deficiency of this ion may or may not be accompanied by decreased serum magnesium levels and may result from increased urinary magnesium losses in children with IDDM.

Adolescent↗
PubMed1997

Dose-dependent effect of octreotide on nitrogen retention and glucose homeostasis in response to endotoxemia in parenterally fed rats.

OBJECTIVE: This study compared the effect of different doses of octreotide on glucose and protein homeostasis in rats receiving concomitant lipopolysaccharide and parenteral nutrition infusions. METHODS: Sixty-six male Sprague Dawley rats (185 to 220 g) were randomized to receive parenteral nutrition only (PN), PN plus continuous infusion of Escherichia coli 026:B6 lipopolysaccharide at 6 mg/kg/day (LPS), PN plus LPS plus octreotide at 10 micrograms/kg/day (LPS + Oct 10), 100 micrograms/kg/day (LPS + Oct 100), or 1000 micrograms/kg/day (LPS + Oct 1000) for 48 hours. Prior to randomization all animals received isocaloric and isonitrogenous PN (170 kcal/kg/day as glucose and 1.1 g N/kg/day) and were kept nil per os except for water ad libitum. Nitrogen balance, urinary 3-methylhistidine/creatinine ratio, serum glucose concentration, and incidence of glycosuria were compared between groups. Serum urea nitrogen (SUN) changes were incorporated into the cumulative 48 hour nitrogen balance. ANOVA, Duncan's multiple range test, and Fisher's Exact Test were used for statistical analysis. RESULTS: Nitrogen balance (mg/48 hours) was significantly lower in all four groups receiving LPS +/- Oct when compared to the control group receiving PN alone. SUN (mg/dL) was significantly higher in all four groups receiving LPS +/- Oct when compared to control. There were no statistically significant differences in nitrogen balance or SUN among the four groups receiving LPS +/- Oct. The ratio of urinary 3-methylhistidine/ creatinine was significantly higher in the LPS + Oct 1000 group compared to the PN group (0.77 +/- 0.37 vs. 0.42 +/- 0.24, p < 0.05). Serum glucose concentrations and incidence of glycosuria among the five groups were not significantly different. CONCLUSIONS: Endotoxin significantly reduces nitrogen balance compared to controls fed PN. Octreotide does not significantly improve nitrogen retention or glucose homeostasis in endotoxemic parenterally fed rats.

Animals↗
PubMed2000

Mice lacking renal chloride channel, CLC-5, are a model for Dent's disease, a nephrolithiasis disorder associated with defective receptor-mediated endocytosis.

Nephrolithiasis (kidney stones) affects 5-10% of adults and is most commonly associated with hypercalciuria, which may be due to monogenic renal tubular disorders. One such hypercalciuric disorder is Dent's disease, which is characterized by renal proximal tubular defects that include low molecular weight proteinuria, aminoaciduria and glycosuria, together with rickets in some patients. Dent's disease is due to inactivating mutations of the renal-specific voltage-gated chloride channel, CLC-5, which is expressed in the proximal tubule, thick ascending limb and collecting duct. The subcellular localization of CLC-5 to the proximal tubular endosomes has suggested a role in endocytosis, and to facilitate in vivo investigations of CLC-5 in Dent's disease we generated mice lacking CLC-5 by targeted gene disruption. CLC-5-deficient mice developed renal tubular defects which included low molecular weight (<70 kDa) proteinuria, generalized aminoaciduria that was more pronounced for neutral and polar amino acids, and glycosuria. They also developed hypercalciuria and renal calcium deposits and some had deformities of the spine. Furthermore, endocytosis as assessed by horseradish peroxidase uptake in the proximal tubule was severely impaired in CLC-5-deficient mice, thereby demonstrating a role for CLC-5 in endosomal uptake of low molecular weight proteins. Thus, CLC-5-deficient mice provide a model for Dent's disease and this will help in elucidating the function of this chloride channel in endocytosis and renal calcium homeostasis.

Animals↗
PubMed1985

Acute response of urinary N-acetyl-beta-D-glucosaminidase to mannitol infusion in the dog.

Urinary activity of N-acetyl-beta-D-glucosaminidase (NAG) has been used as an indicator of subtle renal injury in a variety of conditions. Such enzyme activity has been shown to be increased in human and other animals with diabetes mellitus. The mechanism of this increase in urinary NAG activity is not known. To determine if the osmotic diuretic effect of the glycosuria could stimulate urinary NAG activity, mannitol was infused into the left renal artery of six dogs to cause a unilateral osmotic diuresis and compared to the right side. During three control periods of 20 minutes, each urinary NAG excretion (expressed in units as the ratio of NAG activity to urinary creatinine, NAG/Cr) was equal from both left and right kidneys, 5.0 +/- 1.5 vs 6.0 +/- 3.6 units, respectively. During the 11 mannitol infusion periods urine volume and sodium excretion rose significantly from the left kidney, .50 +/- 2 to 1.5 +/- .3 ml/min and 21 + 5 to 99 +/- 16 u Eq/min, respectively. However urinary NAG/Cr did not change, 5.0 +/- 1.5 to 5.1 +/- 1.0 units. In six control dogs not infused with mannitol, urinary NAG/Cr tended to rise with time from control to experimental collection periods, 4.7 +/- 2.0 to 8.1 +/- 3.0 respectively; however these are not significantly different. In all dogs urine volume and sodium excretion tended to rise throughout the course of the study due to hydration with normal saline; thus it is possible that the tendency for urinary NAG activity to rise may have been due to the increase in sodium excretion. However, these studies demonstrate that the osmotic diuresis induced by mannitol produced no significant change in urinary NAG activity. Thus it may be that the hyperglycemia itself, and not the glycosuria, produces the increase in urinary NAG activity seen in the diabetic.

Acetylglucosaminidase↗
PubMed1999

Prospective evaluation of high-dose ifosfamide-related nephrotoxicity in young adult patients with recurrent osteosarcoma previously treated with cisplatin, methotrexate and standard-dose ifosfamide.

A prospective evaluation of high-dose ifosfamide (IFO)-related nephrotoxicity in adults and young adults previously treated with cisplatin, methotrexate (MTX) and standard-dose IFO was performed. Eighteen patients (median age 22) with recurrent osteosarcoma were studied: 11 were pretreated with MTX, cisplatin and standard-dose IFO, and seven with MTX and cisplatin. The treatment was comprised of four cycles of high-dose IFO (15 g/m2 over 5 days CI) and mesna at equivalent dose with granulocyte colony stimulating factor support. Renal function was assessed before treatment, after each IFO cycle and after chemotherapy completion. Acute nephrotubular damage was always observed after each IFO cycle with significant changes of renal tubular enzymes N-acetyl-beta-D-glucosaminidase, alanine aminipeptidase, urinary excretion and reduction of tubular reabsorption of phosphate. The appearance of glycosuria was related to the cumulative dose received. Transient and reversible renal tubular acidosis was observed in three patients. WHO grade I renal toxicity was observed in two patients. After chemotherapy completion, persistent mild glomerular and nephrotubular impairment was observed in one patient who had also received aminoglycoside antibiotics due to febrile neutropenia. Persistent and mild glycosuria was documented in another patient. No significant changes compared to baseline values were observed in the remaining patients. We conclude that a chemotherapy regimen with high-dose IFO in young adults pretreated with MTX, cisplatin and standard-dose IFO is feasible with a mild, usually reversible, nephrotoxicity.

Adolescent↗
PubMed1995

Growth hormone treatment of short Chinese children with beta-thalassaemia major without GH deficiency.

OBJECTIVE: Despite regular transfusion and desferrioxamine treatment, growth failure is commonly seen in adolescent children with beta-thalassaemia major. The growth failure has been thought to be due to GH resistance rather than GH deficiency. We investigated the effect of GH on short non-GH deficient children with beta-thalassaemia. DESIGN: Recombinant human GH was given in a dose of 0.14 IU/kg/day subcutaneously in an open study. PATIENTS: Fifteen prepubertal Chinese children with beta-thalassaemia major (ranging from 7.16 to 14.7 years in age) with height -1.5 SD or more below the population mean for age and a growth velocity of less than 5 cm/year were treated with growth hormone for one year. All children had peak GH response > 15mlU/l to insulin induced hypoglycaemia and normal thyroid function and adrenal reserve. MEASUREMENTS: Anthropometric measurements were performed every 3 months. Morning urine was tested twice weekly for glycosuria. Blood count, renal and liver function tests, fasting blood glucose, IGF-I and fructosamine levels were assessed at entry and every 3 months during treatment. Fasting insulin was measured before and after 3 and 12 months of GH treatment. Skeletal maturity was assessed before and after one year of treatment. RESULTS: Treatment was stopped in two children after 6 months because of poor growth response and noncompliance with treatment and in one child at 9 months because of bone marrow transplantation. In the 13 children, the growth velocity increased from 3.6 +/- 0.7 cm/year to 8 +/- 1.2 cm/year after one year of GH treatment (P < 0.001). IGF-I was low before treatment (10.1 +/- 2.7 nmol/l), rising significantly to 15.8 +/- 4.8, 18.4 +/- 4.6, 19.3 +/- 6.4 and 21.9 +/- 7.5 nmol/l at 3, 6, 9 and 12 months of treatment (P < 0.005). The mean pretreatment bone age in the 13 children was 9.58 +/- 1.41 years and increased to 10.53 +/- 1.43 years after one year of treatment (delta BA/CA 0.95 +/- 0.3 years). None of the patients developed glycosuria or hypertension. There was no significant change in blood count, renal and liver function, thyroid function, fasting blood glucose or insulin concentrations during treatment. CONCLUSION: Growth failure in these children with normal GH reserve and low serum IGF-I concentrations would suggest GH insensitivity. Supraphysiological doses of exogenous GH can cause a significant increase in serum IGF-I levels and a significant improvement in short-term growth of short children with beta-thalassaemia major.

Adolescent↗
PubMed1988

Predicting future treatment of diabetes mellitus from characteristics available at presentation.

This study was designed to identify the clinical features of a newly diagnosed diabetic patient that are most useful in deciding treatment. A secondary aim was to formulate a statistical model for predicting subsequent treatment. The following features were considered in 289 patients: age, sex, severity and duration of symptoms, degree and duration of weight loss, glycosuria, ketonuria, blood glucose concentration, body mass index (BMI), and family history of diabetes. Three treatment groups, 6 months after diagnosis, were defined: diet alone, diet with oral hypoglycaemic agent(s), and insulin-treated. Univariate analysis showed that symptom severity, glycosuria, ketonuria, glucose concentration, weight loss, and BMI were significantly different between the three groups. Age and rate of weight loss were significantly different between the insulin-treated and non-insulin-treated groups. Multivariate analysis gave a model to calculate the probability of requiring each of the three treatments given certain characteristics. A second cohort of 174 patients was used to assess the accuracy of the model. The model predicted the actual treatment at 6 months correctly in 72%.

Adolescent↗