Metabolic dysfunction in late-puberty adolescent girls with type 1 diabetes: relationship to physical activity and dietary intakes.

AIMS: At puberty, type 1 diabetes (T1D) among young girls can lead to excess body weight, insulin resistance, deterioration of glycaemic control and dyslipidaemia. Although biological factors contribute largely to such metabolic dysfunction, little is known of the role of behavioural factors such as physical activity and diet. METHODS: This study investigated the association between metabolic dysfunction measured after a 12-h overnight fast and behavioural factors, including diet (4-day diary) and physical activity (validated questionnaire), in 19 postmenarchal adolescent girls with T1D compared with 19 healthy girls. RESULTS: T1D girls displayed higher levels of fat mass, insulin resistance (higher plasma glucose, serum leptin and waist-to-hip ratios) and dyslipidaemia (higher LDL-C and apolipoprotein B levels, lower HDL-C and apolipoprotein A-1 levels). Also, contrary to what is usually observed in T1D adults, serum adiponectin, an important vessel protector, was not raised in T1D adolescent girls compared with healthy controls. Quantity and quality of dietary macronutrient intakes as well as physical activity levels were comparable in both groups, although the T1D girls with the poorest metabolic profiles reported having the healthiest diets (fewer total calories, more protein and less carbohydrates). However, in T1D girls, less physical activity and more time spent watching television were associated with poorer metabolic profiles (higher waist-to-hip ratios, fat mass and leptin levels, and lower adiponectin, HDL-C and apolipoprotein A-1 levels). CONCLUSION: Collectively, these data suggest that physical inactivity is linked to metabolic dysfunction to a greater extent than unhealthy dietary habits in postmenarchal T1D adolescent girls.

Alteration in sympathoadrenergic activity at rest and during intense exercise despite normal aerobic fitness in late pubertal adolescent girls with type 1 diabetes.

BACKGROUND: An impaired sympathoadrenergic response to hypoglycaemic episodes has been described in young Type 1 diabetic subjects. It is unknown if this altered response occurs with exercise, and if it could influence aerobic power. METHODS: Body composition (skinfold thickness), physical activity (questionnaire) and aerobic power (PWC170 and VO2max) were assessed in 19 post-menarcheal Type 1 diabetic (T1D) girls (13.3-18.2 years) and 19 healthy siblings. At rest and at each stage of the graded exhaustive exercise, plasma glucose, insulin, epinephrine and norepinephrine, were monitored via an intravenous catheter. RESULTS: Only when expressed per kilograms of body weight, was aerobic power impaired in T1D girls compared to controls, probably because they were overweight. Throughout exercise, plasma glucose remained stable while plasma insulin decreased in the healthy girls, whereas glucose diminished significantly with no change in plasma insulin in T1D girls. During exercise catecholamines increased in the same way in both groups. However, at rest and throughout all stages of exercise, norepinephrine levels were significantly lower by a mean difference of 1.2 nmol/L, while epinephrine levels were significantly higher by a mean difference of 0.14 nmol/L, in T1D girls compared to healthy girls. Heart rates of T1D girls were not affected by the sympathoadrenergic alteration. CONCLUSION: T1D adolescent girls display an altered sympathoadrenergic activity at rest and during intense exercise. Their reduced sympathetic activity, albeit probably compensated for by higher adrenomedullary responsiveness or sensitivity, does not affect their heart rate adaptations to exercise.

Accuracy of physical working capacity 170 to estimate aerobic fitness in prepubertal diabetic boys and in 2 insulin dose conditions.

AIM: Exercise tests evaluate the effects of physical activity, which is one of the four recommendations for diabetes treatment. An adjusted and accurate measure of aerobic capacity in diabetic patients is thus needed. This study compared two estimates of aerobic fitness (maximal oxygen uptake vs physical working activity PWC170, i.e., the workload at a pulse of 170) and the usual versus a reduced insulin dose in preadolescent boys with type 1 diabetes mellitus. METHODS: Sixteen prepubertal type 1 diabetic boys performed a submaximal test, the PWC(170). Gas exchange values and capillary blood glucose levels were monitored and, when possible, the test was extended to exhaustion. In 7 boys, the test was performed twice on separate days. On one day they received their usual insulin dose and on the other, their short-acting insulin was reduced by 1/3; the two tests were held in random order. The 9 other children were tested only once after receiving their usual insulin dose. RESULTS: For the 16 boys who performed the test with the usual insulin dose, PWC(170) (W) and peak oxygen uptake (peak VO(2)) (L.min(-1)) correlated closely (r=0.81, P=0.002). Aerobic fitness did not change with insulin dose, but some hypoglycemic episodes occurred when insulin dose was not reduced. CONCLUSIONS: Since maximal effort does not add more information, routine use of the submaximal peak VO(2)-correlated test, the PWC(170), seems sufficient, possibly in association with a planned insulin dose reduction. This dose change does not interfere with performance, but could reduce the risk of hypoglycemia.

Importance of stromal determinants in the generation of dendritic and natural killer cells in the human spleen.

Summary The interaction between stroma and blood cells in the human spleen has received little attention, despite their well-defined roles during blood cell development in bone marrow. We have reported previously that human spleen-derived fibroblasts display a differentiated myofibroblast phenotype and constitutively express a biologically active form of membrane interleukin (IL)-15 that can drive co-cultured CD34(+) blood cells to differentiate into activated natural killer (NK) cells. Here, we show that, in addition to NK cells, CD34/fibroblast co-cultures also yield myeloid CD1a(+)CD38(+)CD68(+)CD86(+) HLA-DR(+)CD14(-)CD80(-) dendritic cells (DCs) after 3-4 weeks in culture. We found that DC development depended on endogenously secreted stromal macrophage colony-stimulating factor (M-CSF) and CD40/CD40L interaction rather than on fibroblast- and CD34-derived membrane IL-15. CD1a(+) cells were necessary for co-produced NK cells to acquire lytic functions by a mechanism involving cell-to-cell contact and DC-derived IL-12. This study highlights the importance of spleen myofibroblasts in the in vitro generation of two distinct cell types (DC and NK cells) from the innate immune system and suggests that the human spleen is involved in the generation of NK cells from circulating progenitors.

Effects of human fibroblasts from myelometaplasic and non-myelometaplasic hematopoietic tissues on CD34+ stem cells.

Fibroblasts demonstrate different phenotypes and functions according to the tissue of origin and its physiopathologic state. We previously showed that fibroblasts isolated in culture from myelometaplasic (MM) spleen differed phenotypically from fibroblasts from normal bone marrow (BM). We compared the influence of each type of fibroblasts on the behavior of CD34+ stem cells. Expansion of nucleated cells was observed when blood CD34+ cells were co-cultured for 3 weeks with MM spleen-derived fibroblasts in monolayers. Myeloid cell differentiation was also observed as indicated by a decline in CD34+ cells and increases in CD14+, CD15+ and CD41+ cells. This myeloid differentiation was enhanced in the presence of MM spleen compared with normal BM-derived fibroblasts. Similarly, proliferation and differentiation of BM CD34+ cells was better in the presence of BM rather than MM spleen-derived fibroblasts. In addition, fibroblasts from MM spleen also induced a differentiation of CD56+ natural killer (NK) cells whereas BM-derived fibroblasts did not. Overall, the data indicate that cultured fibroblasts from diseased tissue have distinct growth and differentiation regulatory characteristics. They also suggest a role for these cells in hematopoietic disorders.

[Severe streptococcal group A infection complicating varicella]. / Infection sévère à streptocoque du groupe A compliquant une varicelle.

UNLABELLED: Varicella is a common viral infection which is generally benign in infancy and has a good outcome. It may sometimes be complicated by severe group A streptococcal superinfection. CASE REPORT: Three days after the beginning of varicella, a previously healthy 2-year-old girl presented with left leg pain, lameness and edema of all four limbs. Toxic shock syndrome occurred, due to beta-hemolytic group A Streptococcus grown from blood culture. Computerized tomography (CT) scan showed a mild effusion involving both hips. Cefotaxim was administered, but the week after magnetic resonance imaging (MRI) showed a necrotizing fasciitis and a lesion of the left leg leading to a patchy femoral diaphysis consistent with osteomyelitis. Joint aspirate culture did not grow. The left leg was immobilized in plaster for 6 weeks and the child was given cefotaxim and fosfomycin parenterally during 30 days, then followed by 45 days of oral amoxicillin. She recovered without sequelae. CONCLUSION: Group A Streptococcus infection is a dangerous complication of varicella. It must be considered in case of any joint pain occurring during or just after this disease. The choice of the best treatment needs full collaboration between surgeons, radiologists and pediatricians.