Recurrent nightly ketosis after prolonged exercise in type 1 diabetes - the need for glycogen replacement strategies. Case report and review of literature.

Exercise in diabetes patients has many benefits but also several risks, of which hypoglycemia is most often discussed. We present a case with recurrent keto-acidosis post-exercise, in which we hypothesize that glycogen replacement strategies were insufficient. Our experience in this case and review of the literature emphasize the importance of discussing glycogen replacement strategies with your diabetic athletes.

New insights into factors influencing adult height in short SGA children: Results of a large multicentre growth hormone trial.

BACKGROUND: Growth hormone (GH) treatment is effective in improving adult height (AH) in short children born SGA. However, there is a wide variation in height gain, even after adjustment for predictive variables. It is therefore important to investigate new factors which can influence the response to GH. OBJECTIVE: To investigate the efficacy of GH treatment (1 mg/m(2/) day) in short SGA children on AH. To assess the relation between spontaneous catch-up growth after birth and growth during puberty on the total height gain SDS to AH. PATIENTS: Longitudinal GH trial in 170 children. RESULTS: Median age at start of GH was 7·1 years and height -3·0 SDS. AH was -1·8 SDS (TH-corrected AH -1·1 SDS) in boys and -1·9 SDS (TH-corrected AH -1·3 SDS) in girls. Spontaneous catch-up growth after birth was ≥0·5 SDS in 42% of children. In contrast to expectation, spontaneous catch-up growth was negatively correlated with total height gain SDS during GH (P = 0·009). During puberty, height SDS declined (-0·4 SDS in boys and -0·5 SDS in girls) resulting in a lower total height gain SDS than expected. Pubertal height gain was 25·5 cm in boys and 15·3 cm in girls, significantly lower compared to AGA children (P < 0·001). At onset of puberty, BA for boys and girls was moderately advanced (P = 0·02 and P < 0·001, respectively). Growth velocity was comparable to AGA children during the first two years of puberty, but thereafter significantly lower until reaching AH (P < 0·001). CONCLUSION: In contrast to our hypothesis, children with greater spontaneous catch-up growth after birth show a lower total height gain SDS during GH. Height SDS declines from mid-puberty, due to a marked early deceleration of growth velocity.

Long-term non-surgical therapy of severe persistent congenital hyperinsulinism with glucagon.

BACKGROUND: Congenital hyperinsulinism (CHI) is characterized by severe hypoglycemia caused by dysregulated insulin secretion. The long-term outcome is dependent on prevention of hypoglycemic episodes to avoid the high risk of permanent brain damage. Severe cases are usually resistant to diazoxide or nifedipine. In addition, somatostatin analogues are ineffective in a subgroup of patients to achieve stable euglycemia. In these infants the only remaining long-term option has been subtotal pancreatectomy with high risk of diabetes mellitus. Intravenous infusions of glucagon are used as immediate treatment to stabilize euglycemia in affected newborns. The rationale of this treatment comes from the observation of an increased glycogen content of the liver when glycogenolysis is inhibited by insulin. OBJECTIVE: To review the efficacy and safety of long-term subcutaneous glucagon infusion as a potential therapeutic option for blood glucose stabilization in infants with severe CHI without the need of additional intravenous glucose or immediate surgical intervention. METHOD: Retrospective review of 9 children with CHI who received continuous subcutaneous infusion of glucagon for weeks or months. Glucagon was added to octreotide to replace octreotide-induced suppression of endogenous glucagon secretion, thereby liberating glucose by stimulation of hepatic glycogenolysis. In 3 cases, a stabilized formulation of glucagon was used to prevent glucagon crystallization that frequently occurs in smaller volumes. RESULTS: Introduction of glucagon allowed the reduction or discontinuation of central glucose infusion in all children studied. In 2 patients, glucagon was introduced due to recurrent hypoglycemia despite subtotal pancreatectomy. Six out of 9 children were discharged home on this treatment, which their parents were able to continue without further symptomatic hypoglycemia, convulsions or unconsciousness. In 3 children, subcutaneous glucagon was continuously administered for 1-4 years leading to stable euglycemia. However, 2 children with diffuse type still required subtotal pancreatectomy. As a possible side effect, 2 children developed erythema necrolyticum, which resolved after discontinuation of the glucagon infusion. This has been described before in glucagonoma. CONCLUSION: In this retrospective series, combination therapy of low-dose octreotide and subcutaneous glucagon infusion has been effective in preventing hypoglycemic episodes in severe CHI. We propose this may serve as a therapeutic option in place of high rates of glucose infusion through a central venous catheter and as an alternative to subtotal pancreatectomy in diffuse type of CHI.

Down-regulation of hepatic and intestinal Abcg5 and Abcg8 expression associated with altered sterol fluxes in rats with streptozotocin-induced diabetes.

AIM/HYPOTHESIS: Type I diabetes is associated with altered hepatic bile formation and increased intestinal cholesterol absorption. The aim of this study was to evaluate whether altered expression of the ATP-Binding Cassette half-transporters Abcg5 and Abcg8, recently implicated in control of both hepatobiliary cholesterol secretion and intestinal cholesterol absorption, contributes to changed cholesterol metabolism in experimental diabetes. METHODS: mRNA and protein expression of Abcg5 and Abcg8 were determined in the liver and intestine of rats with streptozotozin-induced diabetes and related to relevant metabolic parameters in plasma, liver and bile. RESULTS: Hepatic mRNA expression of both Abcg5 (-76%) and Abcg8 (-71%) was reduced in diabetic rats when compared to control rats. In spite of increased HDL cholesterol, considered a major source of biliary cholesterol, secretion of the sterol into bile relative to that of bile salts was reduced by 65% in diabetic animals. Intestinal mRNA expression of Abcg5 (-47%) and Abcg8 (-43%) as well as Abcg5 protein contents were also reduced in insulin-deficient animals. This was accompanied by a three- to four-fold increase in plasma beta-sitosterol and campesterol concentrations and by a doubling of the calculated apparent cholesterol absorption. These effects partially normalized upon insulin supplementation. CONCLUSION/INTERPRETATION: Our data indicate that effects of insulin-deficiency on bile composition and cholesterol absorption in rats are, at least partly, attributable to changes in hepatic and intestinal Abcg5 and Abcg8 expression.

Postprandial chylomicron clearance rate in late teenagers with diabetes mellitus type 1.

A delayed chylomicron (CM) clearance rate, a known risk factor for atherosclerosis, has been described in adults with diabetes type 1 (DM1). We determined the CM clearance rate in late teenagers with DM1, and the relationship between CM clearance rate and elevated plasma lipid concentrations in DM1 teenagers in poor metabolic control (as characterized by HbA(1c) percentage). Plasma lipids and CM clearance were determined in nine patients with DM1 (mean age +/- SD: 17.5 +/- 0.6 y) and four healthy controls (mean age +/- SD: 20.1 +/- 0.8 y), by measuring breath (13)CO(2), plasma triglyceride, retinyl palmitate, and (13)C-labeled oleic acid concentrations, after oral administration of a fat-rich meal together with vitamin A and (13)C-oleic acid. In patients with DM1, fasting triglyceride and cholesterol concentrations were positively correlated with HbA(1c) percentage (p < 0.05). Neither in DM1 patients, nor in controls, was an elevated triglyceride concentration (above 1.7 mmol/L) found. Yet, in 22% of DM1 patients, cholesterol concentration was above 5.2 mmol/L, but not in any of the controls. CM clearance rate in DM1 patients was similar to that in controls and did not significantly correlate with HbA(1c) percentage. Fasting lipid concentrations in DM1 patients were not significantly correlated with CM clearance rate. Present data indicate that elevated lipid concentrations in late teenagers with DM1 are not attributable to a delay in CM clearance rate. A delayed CM clearance rate at late teenager age is not a risk factor contributing to the increased risk for atherosclerosis in DM1.

Ureaplasma urealyticum colonization, prematurity and bronchopulmonary dysplasia.

The aim of the present study was to determine the association between the presence of Ureaplasma urealyticum in endotracheal aspirates and bronchopulmonary dysplasia (BPD). In addition, a review of similar studies from the English literature is presented. During the period February 1990 until March 1991, 108 mechanically-ventilated infants were included in a prospective study. Endotracheal aspirates were cultured for U. urealyticum. Birth weight, gestational age and development of BPD was recorded. Cultures were positive in 23 infants, resulting in a 21% colonization. The infants with positive cultures had a significantly lower gestational age (mean 28.9 vs 31.5 weeks; range 25-40 vs 25-42 weeks; p=0.0014). A positive U. urealyticum culture was not associated with a low birth weight (mean 1,390 vs 1,690 g; range 675-4,090 vs 700-3,600 g; p=0.0712). A positive U. urealyticum culture was significantly associated with BPD (p=0.0373). However, after correction for gestational age by logistic regression analysis, BPD failed to correlate with the presence of positive U. urealyticum cultures. A MEDLINE search of the English language literature was performed to identify all studies having the association of U. urealyticum colonization and BPD. Fourteen controlled studies were found. Five studies found no significant association between U. urealyticum colonization and BPD. In two studies, after correction for gestational age, the association between U. urealyticum colonization and BPD did not remain significant. In five studies with a significant association between U. urealyticum colonization and BPD, no correction for gestational age had taken place. In conclusion, U. urealyticum colonization is not associated with the development of bronchopulmonary dysplasia. U. urealyticum is often associated with gestational age and/or low birth weight; to investigate the association between U. urealyticum and bronchopulmonary dysplasia correction for both parameters should be made.

[Pyridoxine-dependent epilepsy in an infant]. / Pyridoxine-afhankelijke epilepsie bij een zuigeling.

A newborn girl with seizures was, after repeated conventional anticonvulsive treatment, cured by pyridoxine administration. Pyridoxine-dependent seizures are an uncommon disease with autosomal-recessive heredity and a variable clinical picture. The prognosis may be favourable when diagnosis is made early. Confusion with perinatal asphyxia, and initial good response to usual anticonvulsive treatment can lead to delay in diagnosis.

[Vertebral osteomyelitis in an infant]. / Wervel-osteomyelitis bij een zuigeling.

Neonatal osteomyelitis is uncommon. The disease starts often without signs of infection and may lead to severe complications. A case is reported of a neonate with vertebral osteomyelitis of the cervical vertebrae. Difficulties of diagnosing the disease and several therapeutic regimes proposed in the literature are discussed.

[IgA deficiency: clinical ans immunological evaluation of 28 patients]. / IgA-deficiëntie: klinische en immunologische evaluatie van 28 patiënten.

Seventeen patients with total IgA deficiency and II with partial IgA deficiency were investigated. Symptoms associated with IgA deficiency were retrospectively studied, and the levels of other immunoglobulins were measured in blood and in saliva. The most important associated complaints were recurrent upper respiratory infections. More than 50% of the symptomatic patients recovered clinically, associated with a recovery of the IgA level or with compensatory humoral immunological mechanisms (such as elevated IgG subclasses or strongly positive secretory IgM). The necessary diagnostic procedures, follow-up of patients and families are described.

Fatal ureaplasmal pneumonia and sepsis in a newborn infant.

Ureaplasma urealyticum was isolated in pure culture from blood tracheal aspirate and lung tissue in a newborn infant, who died of a severe pneumonia within 48 h after birth. The clinical course was characterized by persistent pulmonary hypertension of the newborn (PPHN). Post-mortem examination revealed extensive hyaline membrane formation combined with signs of inflammation in both lungs. The clinical and histopathological picture resembled that of early onset group B haemolytic streptococcal pneumonia/sepsis.