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SUMMARY Passive intestinal permeability in 33 newborn babies was studied using feeds containing lactulose and mannitol. Each marker is thought to pass across the gut wall by a different route; lactulose by a paracellular and mannitol by a transcellular pathway. Neither is metabolised and both are wholly and solely excreted by the kidney; urinary recovery is a measure of the intestinal uptake. Babies born before 34 weeks' gestation exhibited a higher intestinal permeability to lactulose than more mature babies, and all preterm babies showed an appreciable decline in lactulose absorption during the first week of oral feeds. Babies of 34 to 37 weeks' gestation achieved a 'mature' intestinal permeability to lactulose within four days of starting oral feeds. These findings may reflect the immaturity of the gut of the preterm baby rather than a process essential to adaptation to enteral nutrition.One of the major challenges faced by the newborn baby is the abrupt transition from parenteral to enteral nutrition. By the third trimester of pregnancy the gut seems to be anatomically prepared,1 but after oral feeding begins, considerable physiological and morphological changes take place.2 These adaptations to extrauterine nutrition all contribute to the major function of the gut-absorption. Presented with food for the first time, however, the gut must distinguish the essential from the harmful, and balance selection with exclusion.

Normal fasting subjects received regular insulin and mixtures of regular with NPH or lente to assess the effects of the combinations on serum insulin concentrations (SIC) and blood glucose responses (BGR). In addition, the influence of concentration, depth, and method and site of administration was investigated. In studies of mixtures of regular with NPH and with lente, it was observed that the regular: lente ratio needed to achieve peak SIC was higher than with the regular: NPH combination. Increased SIC, including either the peak and/or the time interval required to achieve the peak, were related to the depth and site (deltoid and abdominal greater than anterior thigh or buttocks). Assuming linear kinetics of absorption, significant quantities of insulin fail to reach the serum. Marked intra- and intersubject variations in SIC and BGR to regular, NPH, and lente insulins were observed.

Mannitol and lactulose were used as probe molecules to measure intestinal permeability in children with active small-bowel Crohn's disease and with untreated coeliac disease. Mannitol and lactulose were administered by mouth in a moderately hypertonic solution (580 mmol (mosmol)/l), and results were expressed as the ratio of the molecules excreted in urine over five hours. Patients with Crohn's disease had a sixfold increase in permeability (due to increased lactulose permeability) and those with coeliac disease a fivefold increase (due to decreased mannitol permeability).From these results the test offers potential as a noninvasive investigation in children with small-bowel disease. IntroductionHydrophilic molecules permeate the healthy small-bowel mucosa at rates which depend on their molecular size.1 2 In clinical practice various non-metabolised sugars used to study adult populations indicate that in villous atrophy there is a decreased absorption of small molecules and an increased absorption of larger molecules.3 Other studies show that the small-bowel mucosa is more permeable to large molecules in patients with eczema and food allergy5 and also during the neonatal period.6 We were interested in this technique as a non-invasive investigation for children and have evaluated two probe molecules, mannitol and lactulose, to measure intestinal permeability in normal subjects and in two differing conditions of abnormal small-bowel mucosa-untreated coeliac disease and active Crohn's disease.

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Glucose homeostasis in healthy subjects is characterized by postmeal glucose increases of about 40 mg/dl, peaks at about 45 min, decreases close to antecibal levels 1 h after the peak, and no spontaneous oscillations until the next meal. Diabetes is characterized by progressive loss of glucose homeostasis from stable to unstable, which is directly proportional to loss of insulin secretory reserve. Degree of instability of diabetes in ambulatory subjects within a 24-h period can be expressed as mean amplitude of glycemic excursion of M-value and between two successive 24-h periods as mean of daily differences of blood glucose. Stable diabetic persons have lower values, which are closest to those of nondiabetic persons, and unstable diabetic persons have higher values. The mean diurnal blood glucose level is a measure of glycemic control. The failure to restore glycemic patterns of diabetic to those of nondiabetic persons is largely due to the failure of subcutaneously administered insulin to mimic the pattern of insulinemia of healthy subjects.

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