M Kojima

Adiposity Rebound and the Development of Metabolic Syndrome

OBJECTIVE: The age of adiposity rebound (AR) is defined as the time at which BMI starts to rise after infancy and is thought to be a marker of later obesity. To determine whether this age is related to future occurrence of metabolic syndrome, we investigated the relationship of the timing of AR with metabolic consequences at 12 years of age. METHODS: A total of 271 children (147 boys and 124 girls) born in 1995 and 1996 were enrolled in the study. Serial measurements of BMI were conducted at the ages of 4 and 8 months and 1, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12 years, based on which age of AR was calculated. Plasma lipids and blood pressure were measured at 12 years of age. RESULTS: An earlier AR (<4 years of age) was associated with a higher BMI (≥20) and a lipoprotein phenotype representative of insulin resistance. This phenotype consists of elevated triglycerides, apolipoprotein B, and atherogenic index and decreased high-density lipoprotein cholesterol in boys and elevated apolipoprotein B in girls at 12 years of age. The earlier AR was also related to elevated blood pressure in boys. CONCLUSIONS: This longitudinal population-based study indicates that children who exhibit AR at a younger age are predisposed to future development of metabolic syndrome. Therefore, monitoring of AR may be an effective method for the early identification of children at risk for metabolic syndrome.

Association of low‐density lipoprotein particle size distribution and cardiovascular risk factors in children

Aim: The objective of this study was to investigate whether the presence of small, dense lipoproteins, which are thought to be related to the metabolic syndrome caused by insulin resistance, can be predicted by routine serum lipid profiling. Methods: The relationship between low‐density lipoprotein (LDL) particle size and serum lipid levels was analysed in 284 school children (148 boys and 136 girls), aged 7 to 13 y old. LDL particle size was determined by gradient gel electrophoresis. Results: The LDL particle diameter was significantly correlated with the serum levels of high‐density lipoprotein cholesterol (HDL‐C) (r= 0.437, p > 0.001) and triglycerides (TG) (r= 0.432, p 0.001), and with the atherogenic index (AI) [total cholesterol/HDL‐C] (r= 0.450, p > 0.001), while only weak correlations were observed with the serum levels of total cholesterol, apolipoprotein A1 and apolipoprotein B. No significant relationship was observed between LDL particle diameter and the serum LDL‐C level.

Issues in interpreting lipoprotein (a) value as a risk indicator for early cardiovascular disease.

Sir, In their recent study comparing the plasma concentrations, distribution and frequency of lipoprotein (a) [Lp(a)] of children with premature parental and/or grandparental cardiovascular disease (CVD), Dirisamer, et al. (1) reported that it seemed possible to identify children who are at high risk for later CVD either with or without an elevated low-density lipoprotein (LDL) cholesterol level. Contrary to expectation, their data also showed a higher prevalence of increased Lp(a) ( 25 mg/dl) in the control group than in the risk group having a CVD family history; however, the reason for this could not be explained. Here we present our views regarding this point and discuss the issue of estimating Lp(a) values in children as a means of predicting future occurrence of CVD. First, permit us to point out the relationship between LDL particle size and Lp(a) levels. Since a reduction in LDL particle size is closely related to insulin-resistant states, which underlie the progression of atherosclerosis, a reduction in LDL particle size is considered a metabolic marker of insulin resistance (2, 3). In fact, it has been demonstrated that the prevalence of small dense LDL (SDLDL) particles (diameter 25.5 nm) in plasma is increased in patients with CVD, and SDLDL particles have been reported to be present even in children who suffer from obesity or hypertriglyceridemia (4). Persistence of insulin-resistant state from childhood to adulthood may be responsible for the subsequent occurrence of CVD. The relationship between LDL particle size and the Lp(a) levels in 238 schoolchildren aged 8–10 y in our birth cohort is shown in Fig. 1 (5). The method used to measure LDL size has been described in an earlier paper (4). As shown in the figure, the Lp(a) levels seemed to be inversely related to LDL particle size although statistically not significant, and an LDL particle size of less than 25 nm (the definition of small, dense LDL) was associated with a low range of Lp(a) values. Investigation of the relationship between LDL particle size and other atherogenic risk factors showed that body mass index (BMI) and triglyceride values were inversely correlated with LDL particle size and that highdensity lipoprotein (HDL) cholesterol level was positively correlated with LDL particle size. This means that Lp(a) levels do not reflect insulin-resistant metablic states well. Second, we will now touch on the polymorphism of Lp(a), because Lp(a) occurs in more than 10 polymorphic forms (phenotypes) that are dependent on the molecular weight of apolipoprotein(a), which is the main structural component of Lp(a). These polymorphic forms are determined by variations in the apo(a) gene on chromosome 6 (6) and in some reports it is suggested

Effect of testosterone on bone mineral gain: observations of male patients with growth hormone deficiency and normal gonadotropin secretion.

Growth hormone (GH) and sex steroids are the major determinants of bone mineral density (BMD). Over the past several years, the dominant role of androgens in male bone physiology has been increasingly questioned as data have emerged suggesting an important role for estrogens in male skeletal development and homeostasis, but some reports elucidate the effects of androgen on skeletal development and maintenance (1,2,3,4). We consider that more clinical evidence on the effects of androgens on actual bone growth is needed to clarify their possible physiological roles in the regulation of bone formation and mineralization (5). Recently, we encountered three pubertal boys with complete isolated GH deficiency (IGHD) whose cases had been detected and diagnosed after the patient had reached puberty. An analysis of the bone mineral status in these patients allowed us to determine the extention to which testosterone contributes to bone mineral gain in GH deficient children.

A patient with membranoproliferative glomerulonephritis diagnosed by the third biopsy via endocapillary proliferative glomerulonephritis and focal membranoproliferative glomerulonephritis.

We present a girl with type I membranoproliferative glomerulonephritis (MPGN) diagnosed by the third renal biopsy. The first renal biopsy was performed at age 11.2 years after microscopic hematuria (which was revealed by school urinary screening) had persisted for 3 months, along with a low level of serum C3. Pathological examination of the biopsied specimen revealed endocapillary proliferative glomerulonephritis with multiple humps. The serum C3 level increased to within the normal range 2 months after the first renal biopsy, and the microscopic hematuria disappeared at age 12.3. However, microscopic hematuria, proteinuria, and the low serum complement level reappeared at age 12.8. Pathological examination of a further renal biopsy that was performed at age 13.2 revealed focal MPGN with humps. Prednisolone therapy was subsequently initiated. Fluvastatin was added to her treatment regime when she developed hypercholesterolemia at age 13.6 and was continued even after normal cholesterol levels were reestablished. Pathological examination of the third renal biopsy, which was performed at age 15.2, revealed type I MPGN with humps. Serum C3 normalized 6 months after the cessation of prednisolone at age 15.9. It is clinically important that patients with nontypical acute glomerulonephritis should be observed over a long period and repeated renal biopsies should be performed.