Plasma homocysteine levels in children and adolescents with type 1 diabetes

OBJECTIVE: Hyperhomocysteinemia has been established as a risk factor for cardiovascular disease. The objective was to investigate total plasma homocysteine concentrations in children and adolescents with type 1 diabetes and a control group. METHOD: Twenty-seven children with type 1 diabetes and 27 subjects of an age- and sex-matched control group were recruited. Fasting samples were collected for plasma total homocysteine, serum vitamin B12, folate, and creatinine. RESULTS: Fasting total homocysteine concentrations showed no difference between patients and controls (5.6 +/- 2.9 micromol/L vs 5.7 +/- 2.2 micromol/L; p greater than 0.05). The diabetic patients had significantly higher serum folate than the healthy controls (11.4 +/- 3.3 ng/mL vs 9.4 +/- 4.1 ng/mL; P = 0.02 and higher serum B12 than the control group (282.8 +/- 119 pg/mL vs 228.5 +/- 50.9 pg/mL; P = 0.03). Total plasma homocysteine concentration correlated with age (r = 0.44, P = 0.02), weight (r = 0.56, P = 0.002), body mass index (r = 0.57, P = 0.002), folate (r = -0.48, P = 0.01), and creatinine (r = 0.41, P = 0.03) in diabetic patients. In stepwise multivariate regression model for diabetics, the independent correlates for total plasma homocysteine concentration was folate (P = 0.002). CONCLUSION: We concluded that fasting plasma total homocysteine concentrations were within normal limits in children and adolescents with type 1 diabetes who were without any clinical evidence of microvascular and macrovascular complications.     

Plasma total homocysteine increases from day 20 to 40 in breastfed but not formula-fed low-birthweight infants

Homocysteine is an intermediate in the folate cycle and methionine metabolism. This study investigated whether formula-fed infants have different plasma total homocysteine to their breastfed counterparts, and during what period any difference developed. Plasma total homocysteine was determined in 53 formula-fed and 15 breastfed healthy low-birthweight babies (< or = 2500 g) around days 10, 20 and 40. Total homocysteine was also measured in human milk. Mean +/- SD plasma total homocysteine levels (micromol l(-1)) at days 10, 20 and 40 were 6.4 +/- 2.6, 6.7 +/- 2.4 and 9.1 +/- 2.4 (breastfed), and 7.5 +/- 3.2, 7.3 +/- 2.1 and 7.4 +/- 1.6 (formula-fed). Homocysteine of breastfed babies at day 40 was higher than that of breastfed babies at day 20 (p < 0.0001), and that of formula-fed counterparts at day 40 (p = 0.002). Homocysteine correlated negatively with formula (day 10) and breast milk (day 40) volume intakes. Median (range) homocysteine in 12 mature human milk samples was 0.30 (not detectable to 0.7) micromol l(-1). Conclusion: Increasing plasma total homocysteine in breastfed babies to higher levels compared with formula-fed babies may be caused by a gradually developing suboptimal B-vitamin status in lactating women.     

Early changes in 24-hour ambulatory blood pressure are associated with high normal albumin excretion rate in children with type 1 diabetes mellitus

OBJECTIVE: The relationship between urinary albumin excretion rate (AER) and elevated blood pressure (BP) is unclear as a cause-effect phenomenon in the development of diabetic nephropathy. The aim of this study was to examine the association between AER, HbA1c and BP in children with normoalbuminuria. METHODS: 24-hour ambulatory BP assessment was performed in 78 children with type 1 diabetes mellitus (DM1), age mean +/- SD 13.4 +/- 2.7 yr, range 7.3-18.3 yr, DM1 duration mean +/- SD 6.6 +/- 2.9 yr, range 2.1-11.9 yr. Using generalised linear mixed models with systolic (SBP) and diastolic (DBP) blood pressure as dependent variables, the effects of AER and HbA1c were examined, adjusting for age, gender, DM1 duration and insulin dose. RESULTS: Patients with high normal AER (7-20 microg/min) had higher SBP during daytime and night-time compared to the low normal AER (< or = 7 microg/min) (mean +/- SD 118.20 +/- 7.98 and 110.33 +/- 7.08 mm Hg, p = 0.02; mean +/- SD 108.76 +/- 9.21 and 100.20 +/- 7.75 mm Hg, p = 0.03, respectively). DBP was also higher both during day- and night-time when compared to the < or = 7 microg/min group (mean +/- SD 73.40 +/- 6.50 and 64.86 +/- 5.67 mm Hg, p = 0.002; mean +/- SD 62.50 +/- 6.75 and 56.30 +/- 5.56 mm Hg, p = 0.03 day- and night-time, respectively). CONCLUSION: A rise in SBP and DBP is associated with increased levels of AER even within the normal range.     

Diabetes complication screening in 937 children and adolescents.

Results are presented of diabetes complication screening in children and adolescents aged 6-20 years. Their diabetes duration was 0.02-18.4 yr and median HbA1c over the preceding 36 months was 8.4% [IQR 7.8-9.3]. Gradable retinal photographs were obtained in 937: 110 less than 11 years (< 11 yr Gp). Albumin excretion rate (AER) was obtained from 3 timed overnight urine collections in 691: 100 in < 11 yr Gp. Early retinopathy was found in 27% (9% in < 11 yr Gp). Microalbuminuria (AER > or = 20 micrograms/min) was found in 4%. Significant individual risk factors for both complications were higher blood pressure, cholesterol, HbA1c, pubertal staging, older age and longer diabetes duration. Using multiple logistic regression, significant risk factors for retinopathy were longer duration and older age and in addition higher HbA1c. Diabetes complication screening detected early subclinical disease in children and adolescents who may benefit from lowering blood pressure and improving metabolic control. Screening should commence after five years of duration in young children, and after two years of duration in adolescents.     

Plasma homocysteine levels and folate status in children with sickle cell anemia.

PURPOSE: A sensitive inverse relationship between plasma homocysteine concentration and folate status has been demonstrated. Although children with sickle cell anemia (SCA) are at potential risk for folate deficiency, plasma homocysteine levels have not been reported in such patients. Therefore, a study was designed to assess plasma homocysteine levels as a marker of folate status. DESIGN: Plasma homocysteine concentrations were measured in 120 children with SCA (102 in steady state and 18 during an acute complication) who had never received supplemental folic acid. Folate status was directly assessed in 34 of these patients. RESULTS: Plasma homocysteine levels in the patients with SCA and control subjects were similar. The mean value +/- 1 SD was 5.8+/-2.5 micromol/L (range, 1.6 to 14.1 micromol/L) in the patients with SCA and 6.1+/-2.7 micromol/L (range, 1.7 to 15.3 micromol/L) in 73 pediatric control subjects. In a subpopulation of the study group (34 children), simultaneous serum folate, red cell folate, and total homocysteine concentrations were also measured. Their serum folate and red cell folate concentrations were normal: 12.4+/-10.0 nmol/L (range, 1 to 42 nmol/L) and 604+/-374.7 nmol/L (range, 205 to 1741 nmol/L), respectively. There was no correlation of plasma homocysteine concentration with various clinical or laboratory measures or with red cell folate concentration. CONCLUSION: Folate stores in children with SCA not receiving folic acid supplements are adequate despite an underlying hemolytic anemia.     

窒息新生儿血清同型半胱氨酸与叶酸的变化

目的：探讨血清中高同型半胱氨酸（Hcy）血症及低叶酸水平与新生儿窒息的发生是否具有相关性,并对性别、胎龄等因素对血清中同型半胱氨酸及叶酸水平是否有一定影响进行分析。方法：应用酶联免疫吸附实验方法检测血清中Hcy水平,应用放射免疫法测定血中叶酸浓度。结果：①与无窒息对照组相比, 新生儿窒息患儿血清Hcy水平显著升高,而叶酸水平显著降低;②窒息组男婴血清Hcy、叶酸水平分别为15.82 ±2.51 μmol/L; 2.49 ±0.19 ng/mL,女婴为10.50±2.19 μmol/L; 2.38±0.40 ng/mL,男、女婴之间比较差异无显著性;③窒息组足月儿血清Hcy、叶酸水平为12.34 ±2. 01 μmol/L,2.58 ±0.19 ng/mL;早产儿为21.25±5.01 μmol/L; 2.14±0.34 ng/mL。早产儿Hcy水平显著高于足月儿（P<0.05）。结论：①新生儿窒息与血清Hcy及叶酸水平具有显著相关性。②血清Hcy及叶酸水平在性别上无显著差异。③缺氧窒息合并早产者血清Hcy水平升高最为显著。     

The prevalence of microalbuminuria in diabetic children and adolescents and its relation to puberty

The albumin excretion rate (AER) was studied in two groups of diabetic children and adolescents. Twenty-four-hour AER was studied in 75 children with diabetes for 5 years, in 49 children with diabetes for 10 years, in 55 children with diabetes for 10-20 years and in 21 age matched healthy controls. Overnight AER was studied in 129 diabetic children and adolescents with a duration of diabetes varying from 1-14 years. Diabetics exhibited a wide range of AER-values and when expressed per body surface area, diabetic children had significantly higher AER compared to controls. Log transformed AER-values were significantly correlated to age and body surface area in diabetics but not in controls. In the diabetics, log AER was also correlated to systolic and diastolic blood pressure but not to HbA1c. 20% of the diabetics had AER values exceeding the upper value for healthy controls which was 18.5 micrograms/min. 31/35 of them were older than 12 years. In both groups of diabetics, 5% had AER-values exceeding those reported to be predictive for later development of overt nephropathy, the youngest being 16 years old. When comparing diabetic children 0-12 years (i.e. before the maximal growth spurt of puberty) to those older than 12 years, at the same duration of diabetes, the latter group had significantly higher AER-values. No sex difference was found in either age group. It is concluded that after puberty diabetic patients also show evidence of incipient diabetic nephropathy. Thus, routine screening for microalbuminuria is recommended also in pediatric diabetes care after 12 years of age.     

Renal functional changes in relation to hemodynamic parameters during exercise test in normoalbuminuric insulin-dependent children

AIM: To examine the relationship between filtration fraction and systemic vasculopathy, in normoalbuminuric insulin-dependent diabetic adolescents. METHODS: We calculated filtration fraction from measured glomerular filtration rate and renal plasma flow during a hypotonic saline perfusion test in 30 normotensive adolescent diabetic patients (9-19 years), with a mean duration of diabetes of 7.4 years. Blood pressure and heart rate were measured in basal conditions, during a 24-h ambulatory monitoring and during a dynamic exercise test on a cycle ergometer and peripheral vascular resistance was calculated. RESULTS: Filtration fraction was increased in the diabetic children compared with controls (30+/-6% vs. 22+/-4%, p<0.001), while renal plasma flow was significantly lower (453+/-133 mL/min/1.73 m2 vs. 593+/-155 mL/min/1.73 m2, p<0.001). Peripheral vascular resistance was significantly higher at peak exercise in diabetic children compared to controls (16.3+/-1.3 mmHg/L min m2 vs. 11.4+/-0.5 mmHg/L min m2, p<0.01). CONCLUSION: These results indicate that in young patients with IDDM, without apparent nephropathy or apparent systemic vasculopathy, filtration fraction is increased, suggesting an increased intraglomerular pressure. The associated reduced decrease of peripheral vascular resistance (increased diastolic blood pressure during exercise) suggests that renal functional abnormalities may be partly explained by a systemic vasculopathy, also present in the kidney.     

Methylenetetrahydrofolate reductase and methionine synthase reductase gene polymorphisms and protection from microvascular complications in adolescents with type 1 diabetes

Abstract:  Folate status has been associated with endothelial dysfunction in adolescents with type 1 diabetes, and elevated total plasma homoocyst(e)ine (tHcy) is a risk for vascular disease in the non-diabetic population. Polymorphisms in genes involved in folate and homocysteine metabolism are implicated in vascular disease. We aimed to determine whether polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) genes are risk factors for early microvascular disease in a large group of adolescents with type 1 diabetes. Four hundred and eighty adolescents were screened annually for retinopathy and microalbuminuria for a median of 4 yr. Molecular analysis for the polymorphisms 677C→T, 1298A→C in MTHFR, and 66A→G in MTRR was performed. The MTRR 66GG genotype reduced the risk for elevated albumin excretion rate (AER) (OR 0.47, CI 0.25, 0.88, p = 0.018) and showed a trend to reduced risk for microalbuminuria (OR 0.27, CI 0.06–1.21, p = 0.09). Survival without elevated AER was increased with the MTRR 66GG genotype (12.4 vs. 9.7 yr, p = 0.04) and with the MTHFR 1298CC genotype (15.2 vs. 10.2 yr, p = 0.007). Conversely, survival without retinopathy was reduced with the MTHFR 677TT and MTRR 66GG combined genotype (6.2 vs. 10.2 yr, p = 0.015). The MTRR 66GG and MTHFR 1298 CC genotypes may confer protection against early nephropathy, possibly because they are associated with lower tHcy. The MTHFR 677 TT was only related to earlier onset retinopathy in combination with MTRR 66GG.     

Plasminogen activator inhibitor-1 and tissue-plasminogen activator in minority adolescents with type 2 diabetes and obesity

Increased plasminogen activator inhibitor-1 (PAI-1) and decreased tissue-plasminogen activator (t-PA) activities lead to impaired fibrinolysis, which is critical for cardiovascular disease. We studied these hemostatic factors at fasting state and after an oral fat load in 12 type 2 diabetic and 17 nondiabetic obese adolescents, matched for age, sex, body mass index, and sexual maturation. Plasma PAI-1, t-PA, and glucose as well as serum C-peptide, insulin, total cholesterol, triglyceride, and HDL and LDL cholesterol levels were measured at 0, 2, 4, and 6 h after the fat load. Metabolic responses were expressed as the area under the curve (AUC). PAI-1 activities were significantly greater in patients than in control subjects [fasting, 23.4 +/- 2.6 versus 12.9 +/- 2.0 U/mL (p < 0.004); AUC, 101.7 +/- 12.1 versus 57.6 +/- 6.5 U . h [corrected] . mL(-1) (p < 0.003)]. Fasting t-PA activities were significantly lower in the patients than in the control subjects (0.8 +/- 0.3 versus 6.5 +/- 2.7 U/mL; p < 0.001). Triglyceride was the only lipid parameter that was significantly different in the patients than in the control subjects [fasting, 1.5 +/- 0.2 versus 0.9 +/- 0.1 mM (p < 0.05); AUC, 15.7 +/- 2.9 versus 7.9 +/- 0.6 mmol . h(-1) . L(-1) (p < 0.02)]. The PAI-1 activities decreased significantly during the loading tests (p < 0.0001), whereas the t-PA activities did not change. Insulin resistance estimated by the homeostasis model assessment was greater in the patients than in the control subjects (14.4 +/- 2.8 versus 4.6 +/- 0.7; p < 0.0001). We conclude that elevated PAI-1 and diminished t-PA activities, suggestive of suppressed fibrinolysis, are present in our adolescents with type 2 diabetes; adding another risk factor for cardiovascular disease and acute high fat load does not further negatively affect this suppressed fibrinolysis.     

The Prevalence of Microalbuminuria in Diabetic Children and Adolescents and Its Relation to Puberty

The albumin excretion rate (AER) was studied in two groups of diabetic children and adolescents. Twenty-four-hour AER was studied in 75 children with diabetes for 5 years, in 49 children with diabetes for 10 years, in 55 children with diabetes for 10–20 years and in 21 age matched healthy controls. Overnight AER was studied in 129 diabetic children and adolescents with a duration of diabetes varying from 1–14 years. Diabetics exhibited a wide range of AER-values and when expressed per body surface area, diabetic children had significantly higher AER compared to controls. Log transformed AER-values were significantly correlated to age and body surface area in diabetics but not in controls. In the diabetics, log AER was also correlated to systolic and diastolic blood pressure but not to HbA_1c. 20% of the 0 diabetics had AER values exceeding the upper value for healthy controls which was 18.5 μg/min. 31/35 of them were older than 12 years. In both groups of diabetics, 5% had AER-values exceeding those reported to be predictive for later development of overt nephropathy, the youngest being 16 years old. When comparing diabetic children 0–12 years (i.e. before the maximal growth spurt of puberty) to those older than 12 years, at the same duration of diabetes, the latter group had significantly higher AER-values. No sex difference was found in either age group. It is concluded that after puberty diabetic patients also show evidence of incipient diabetic nephropathy. Thus, routine screening for microalbuminuria is recommended also in pediatric diabetes care after 12 years of age.     

Urinary N-acetyl-beta-D-glucosaminidase activity in type I diabetes mellitus

We measured urinary albumin excretion rate (AER) and N-acetyl-beta-D-glucosaminidase (NAG) activity in relation to disease duration, acetylated hemoglobin (HbA1c), hypertension and puberty in 44 children and adolescents with type 1 diabetes mellitus. AER and Urinary NAG activity were significantly higher in the patients compared to controls (AER 19.4 +/-; 35.8 vs 4.7 +/- 4.4, NAG activity 5.6 +/- 0.6U vs. 1.6 +/- 0.2U). Microalbuminuria was present in seven patients (15.9%), all of whom were pubertal. There was no correlation between AER and urinary NAG activity. There was a significant direct correlation between AER and disease duration (P <0.05), HbA1c (P < 0.05), diastolic blood pressure (P <0.05) and puberty (P <0.05). None of the microalbuminuria related variables was significantly correlated with urinary NAG activity. Puberty was an independent factor for elevated urinary NAG activity. This study shows that urinary NAG is elevated in children and adolescents with type 1 diabetes mellitus, but is not associated with AER related factors except for puberty. Urinary NAG activity does not appear to be a useful marker for early detection of diabetic nephropathy in children and adolescents with type 1 diabetes mellitus.     

Serum total homocysteine concentrations in children and adolescents in Jos, Nigeria

BACKGROUND: Although the elevation of circulating total serum homocysteine (tHcy) concentration in a fasting state is associated with an increased risk of occlusive vascular disease in adults, the levels in children in Nigeria are not known. AIM: The goals of this study were to describe the distribution of tHcy among a representative sample of children and adolescents in Jos, Nigeria, and to test for differences in tHcy among sex and age categories. METHODS: The sampling scheme, which included persons aged 10 to 19 years, was a stratified, multistage probability design. This cross sectional study involved 182 school children drawn from secondary schools in Jos, Nigeria between January and July 2003. Fasting venous samples were collected and assayed for tHcy, Total protein and Albumin. Anthropometric measurements were taken. RESULT: The mean tHcy concentrations were 2.7 +/- 2.4 (95% CI 2.4-2.9), 3.5 +/- 3.2 (3.3-3.8) and 3.6 +/- 3.2 (3.3-4.1), 4.1 +/- 3.6 (4.0-4.4) micromol/l for the girls and boys aged 10-14 and 15-19 years, respectively. Albumin levels correlate positively with plasma total homocysteine, tHcy (r = 0.45, P = 0.03). CONCLUSION: This study provided age-specific data regarding tHcy concentrations between 10-19 years population in Jos, Nigeria. The tHcy concentration increased as a function of age in both sexes.     

Coronary artery calcification, serum lipids, lipoproteins, and peripheral inflammatory markers in adolescents and young adults with type 1 diabetes

OBJECTIVE: To determine whether coronary artery calcification (CAC), elevated fasting lipids, and lipoproteins and peripheral inflammatory markers are present in insulin-dependent diabetic adolescents and young adults several years after diagnosis. STUDY DESIGN: Hispanic insulin-dependent diabetics (n = 32) diagnosed a mean of 7.8 +/- 4.5 years ago (range, 3 to 16 years), with a mean glycosylated hemoglobin concentration at the time of the study of 8.8% +/- 2.3% and a mean chronological age of 16.1 +/- 4.4 years, were evaluated. Healthy patients (n = 15) with a chronological age (CA) of 15.2 +/- 2.2 years served as control subjects. CAC was assessed by multiple slice computed tomography, and total CAC score in Agatston units was calculated. Fasting lipids, C-reactive protein, apolipoprotein (Apo) A, Apo B, and metalloproteinase-9 (MMP-9) concentrations were measured in all subjects. RESULTS: Neither adolescents with type 1 diabetes nor healthy control subjects presented with evidence of CAC. Fasting lipids, Apo A, Apo B, CRP, and MMP-9 concentrations were similar between diabetic subjects and control subjects. However, 34.4% and 25.0% of our type 1 diabetic subjects had elevated total and LDL cholesterol levels (>200 and >130 mg/dL, respectively), whereas 15.6% and 28.1% had elevated triglyceride and Apo B concentrations (>150 mg/dL and >100 mg/dL, respectively). In addition, 28.1% and 34.4% presented with elevated CRP and MMP-9 levels (>2 mg/L and >80 ng/mL, respectively). Total, LDL and HDL cholesterol, triglycerides, Apo B, CRP, and MMP-9 concentrations correlated positively with duration of the disease and with glycosylated hemoglobin levels. CONCLUSIONS: Although the study adolescents with type 1 diabetes did not present any radiologic evidence of CAC at this stage of the disease, they remain a high-risk group for the development of microvascular and macrovascular artery disease, as risk factors such as elevated lipoproteins and proinflammatory markers are already present in a significant percentage of patients studied.     

Insulin resistance of puberty in African-American children: lack of a compensatory increase in insulin secretion

Type 2 diabetes has been increasing in children, mostly affecting minority populations at around the age of puberty. Despite a multitude of studies demonstrating pubertal insulin resistance/hyperinsulinemia in white children, data are almost non-existent in African-American children. The aim of the present study was to investigate the impact of puberty on glucose metabolism, insulin sensitivity and secretion in African-American children. Twenty prepubertal and 16 pubertal African-American subjects participated. All underwent a 3-h hyperinsulinemic (40 mU/m(2)/min) euglycemic clamp to determine insulin-stimulated glucose disposal, and a 2-h hyperglycemic (12.5 mmol/L) clamp to assess first- and second-phase insulin secretion. Body composition was assessed by dual energy X-ray absorptiometry (DEXA) and visceral and subcutaneous abdominal adiposity with computed tomography (CT) scan at L4-L5. Total glucose disposal, glucose oxidation and non-oxidative glucose disposal were significantly lower in the pubertal group compared with the prepubertal one (53.8 +/- 3.9 vs. 72.2 +/- 5.0 micromol/kg/min, p = 0.009; 23.3 +/- 1.1 vs. 31.6 +/- 1.7 micromol/kg/min, p = 0.001; and 30.0 +/- 3.3 vs. 40.5 +/- 3.9 micromol/kg/min, p = 0.049, respectively). Insulin sensitivity was approximately 30% lower in the adolescents compared with the prepubertal children. However, first- and second-phase insulin secretions were not different between the two groups (971.4 +/- 180.6 vs. 1044.0 +/- 191.4 pmol/L and 999.6 +/- 159.6 vs. 955.8 +/- 142.2 pmol/L, respectively). In conclusion, despite approximately 30% lower insulin sensitivity in African-American adolescents compared with prepubertal children, insulin secretion is not higher. This is in contrast to published findings in white children in whom insulin secretion is higher during puberty. These racial differences in physiologic adaptation to puberty could play a role in the higher prevalence of type 2 diabetes in African-American children at the time of puberty.     

Homocysteinemia, serum folate and vitamin B12 in very young patients with diabetes mellitus type 1

BACKGROUND: Recently a link between hyperhomocysteinemia [HH(e)] and diabetic micro- and macrovascular complications has been reported. However, it is far from clear whether HH(e) is an epiphenomenon or a cause of angiopathic complications. OBJECTIVE: To try to clarify this question we studied adolescents and young diabetic patients without or with only initial complications. SUBJECTS: Plasma levels of basal homocysteinemia [H(e)], folate and vitamin B12 were measured in 76 young diabetic patients (age range 13.6-32.2 yr) and 70 normal volunteers matched for sex and age. In 68 diabetic patients and 53 controls we evaluated the levels of homocysteinemia 2 h after a methionine-loading test. METHODS: Total (free + protein bound) plasma H(e) level was measured by HPLC. RESULTS: Basal or post-load HH(e) occurred in 4.1% of diabetic patients and 12.4% of controls (frequencies not statistically different). In diabetic patients plasma homocysteine values were statistically lower than in controls, but this difference was present only in females. The females showed lower homocysteine values and higher folate levels than males only in the diabetic group. We did not find significant differences in H(e) levels between patients with early complications, late complications or without complications of any type. CONCLUSIONS: Considering very young diabetic patients, the risk of hyperhomocysteinemia does not appear to be greater than in normal controls. Furthermore, our data seem to demonstrate that HH(e) is not a preexisting condition in diabetic patients, even in those predisposed to early complications.     

Dietary nucleotides modulate mitochondrial function of intestinal mucosa in weanling rats with chronic diarrhea

BACKGROUND: Chronic diarrhea during early infancy is characterized by intestinal mucosal injury, and as a consequence, the mitochondrial system of oxidation and reduction and energy production is altered. Since dietary nucleotides have been associated with the process of intestinal mucosal repair in rats with chronic diarrhea, the aim of this study was to examine the effects of dietary nucleotides on the functioning of mucosal mitochondria. METHODS: Weanling rats were fed with a semipurified synthetic diet (C) or the same diet in which carbohydrates were substituted by lactose (L), resulting in chronic diarrhea. During recovery, rats were fed with the semipurified synthetic diet (LC) or the same diet supplemented with nucleotides (LN). The activities of adenosine triphosphate synthase (ATPase), cytochrome c oxidase, citrate synthase, and malate dehydrogenase were measured in mitochondria from ileum and colon mucosa. RESULTS: These enzymatic activities rose in rats with chronic diarrhea, possibly to compensate for the drastic decline in adenosine triphosphate (ATP) synthesis. Dietary nucleotide supplementation allowed normalizing of the activities of ATPase (C: 0.37 +/- 0.16 microg/min/mg protein; L: 0.68 +/- 0.25 microg/min/mg protein; LC: 0.60 +/- 0.20 microg/min/mg protein; LN: 0.42 +/- 0.22 microg/min/mg protein), citrate synthase (C: 0.12 +/- 0.05 mM/min/mg protein; L: 0.21 +/- 0.07 mM/min/mg protein; LC: 0.21 +/- 0.06 mM/min/mg protein; LN: 0.12 +/- 0.02 mM/min/mg protein), and malate dehydrogenase (C: 0.77 +/- 0.48 mM/min/mg protein; L: 3.08 +/- 0.85 mM/min/mg protein; LC: 2.11 +/- 0.44 mM/min/mg protein; LN: 1.13 +/- 0.51 mM/min/mg protein) in the ileum mitochondria of the diarrheic rats. In colonic mucosa, mitochondrial enzymatic activities were restored after eliminating lactose from the diet. CONCLUSION: These results suggest that dietary nucleotides promote earlier restoration of the ileal mitochondrial function after chronic diarrhea.     

Hyperhomocysteinaemia in a coeliac disease heterozygote for the two common mutations (677C->T and 1298A->C) of the methylenetetrahydrofolate reductase gene. Case report

A 17 year old girl with coeliac disease was found to have hyperhomocysteinaemia (fasting plasma total homocysteine concentration - 19.93 micromol/L; N<12.75 micromol/L). At the age of 1 5 she gave up gluten-free diet and had only subtle signs of chronic malabsorption such as folic acid and iron deficiency. The patient was heterozygote for both common mutations (677C->T and J298A->C) of the methylenetetrahydrofolate reductase gene. On gluten diet an intake of 5 mg folic acid/d from supplements for two weeks resulted in an increase in serum folate and a reduction in homocysteine concentration (13.20 micromol/L). The patient continued to consume a gluten containing diet and 0.5mg folic acid/d from supplements for 4 months and homocysteiene decreased to 12.1 mmol/L. Hyperhomocysteinaemia - a cardiovascular and obstetrical risk factor - might be a significant problem for patients with celiac disease on gluten-containing diet.     

Low risk of overt nephropathy after 24 yr of childhood-onset type 1 diabetes mellitus (T1DM) in Norway

AIM: To estimate the risk of diabetic nephropathy and associated risk factors in a nationwide cohort of childhood-onset type 1 diabetes mellitus (T1DM) and 19-30 yr of diabetes duration. METHODS: Patients diagnosed with childhood-onset T1DM (<15 yr) from 1973 through 1982, who previously (1989-1990) participated in a clinical examination to assess diabetic complications, were invited for a new examination in 2002-2003. Of 355 eligible patients, 299 participated (84.2%), and complete urine samples for evaluation of albuminuria were obtained from 295 patients, with a mean age of 33 yr (range 20.9-44.0) and mean diabetes duration of 24 yr (range 19.3-29.9). Persistent microalbuminuria and overt nephropathy [albumin excretion rate (AER) 15-200 microg/min and AER > 200 microg/min, respectively] in at least two out of three consecutive overnight urine samples were defined as diabetic nephropathy. RESULTS: Overt nephropathy was found in 7.8% [95% confidence interval (CI) 4.7-10.9] and persistent microalbuminuria in 14.9% (95% CI 10.8-19.0) of the subjects. Hemoglobin A1c (HbA1c) (p = 0.001), systolic blood pressure (BP) (p = 0.002), total cholesterol (p = 0.019), and C-reactive protein (CRP) (p = 0.019) were associated with diabetic nephropathy. Significant predictors in 1989-1990 for the development of diabetic nephropathy in 2002-2003 were HbA1c (p < 0.001), AER (p = 0.007), and cholesterol (p = 0.022). CONCLUSIONS: In a subgroup of patients diagnosed with childhood-onset T1DM in 1973-1982, 7.8% had overt nephropathy after 19-30 yr of diabetes duration, which is low compared with studies from other countries. HbA1c, systolic BP, total cholesterol, and CRP were each independently associated with diabetic nephropathy.     

Homocysteine in a multi-ethnic sample of school-age children

Cardiovascular disease is a major cause of morbidity and mortality in the United States and other developed countries; arterial lesions that are precursors of disease begin during childhood. Homocysteine levels have been associated with cardiovascular disease rates in adults, but information about levels in and impact on children is limited, particularly among various ethnic groups. This study examined the cardiovascular risk factors of a multi-ethnic sample of 100 9-15 year-old Native American, Hispanic, White, and mixed race children in rural central Washington. The mean fasting homocysteine level was 5.82 micromol/l (+/- 1.47), with no significant differences noted among ethnic groups. Mean dietary intake of folate, vitamin B6, and vitamin B12 exceeded current Recommended Dietary Allowances. Homocysteine levels did not show statistically significant correlations with cardiovascular risk factors. Homocysteine levels were not found to be a cardiovascular risk factor of importance, nor were significant ethnic differences found, in Native American, Hispanic and White children consuming adequate diets.