Part I. Malnutrition in the pediatric population.
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Anthropometry↗
Biomedical subjects
W F Schwenk
Publications and source records attributed to W F Schwenk.
Part IV. Enteral nutrition support.
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Adult↗
Type I diabetes mellitus does not alter initial splanchnic glucose extraction or hepatic UDP-glucose flux during enteral glucose administration.
AIMS/HYPOTHESIS: Our aim was to determine whether an alteration in splanchnic glucose metabolism could contribute to postprandial hyperglycaemia in people with Type I (insulin-dependent) diabetes mellitus. METHODS: Splanchnic glucose extraction, hepatic glycogen synthesis and endogenous glucose production were compared in 8 Type I diabetic patients and in 11 control subjects. Endogenous hormone secretion was inhibited with somatostatin while insulin (approximately 550 pmol/l) and glucagon (approximately 130 ng/l) concentrations were matched with exogenous hormone infusions. Glucose containing [3-3H] glucose was infused into the duodenum at a rate of 20 micromol.kg(-1).min(-1). Plasma glucose concentrations were maintained at about 8.5 mmol/l in both groups by means of a separate variable intravenous glucose infusion. RESULTS: Initial splanchnic glucose uptake, calculated by subtracting the systemic rate of appearance of [3-3H] glucose from the rate of infusion of [3-3H] glucose into the duodenum, did not differ in the diabetic and non-diabetic patients (4.1 +/- 0.8 vs 3.0 +/- 1.0 micromol/kg/min). In addition, hepatic glycogen synthesis, measured using the acetaminophen glucuronide method did not differ (10.7 +/- 2.4 vs 10.1 +/- 2.7 micromol.kg(-1).min(-1)). On the other hand, suppression of endogenous glucose production, measured by an intravenous infusion of [6,6-2H2] glucose, was greater (p < 0.05) in the diabetic than in the non-diabetic subjects (1.7 +/- 1.6 vs 5.8 +/- 1.9 micromol.kg(-1).min(-1)). CONCLUSION/INTERPRETATION: When glucose, insulin and glucagon concentrations are matched in individuals with relatively good chronic glycaemic control, Type I diabetes does not alter initial splanchnic glucose uptake of enterally delivered glucose or hepatic glycogen synthesis. Alterations in splanchnic glucose metabolism are not likely to contribute to postprandial hyperglycaemia in people with well controlled Type I diabetes.
Blood Glucose↗
Subtotal pancreatectomy for hypoglycemia due to congenital hyperinsulinism: long-term follow-up of neurodevelopmental and pancreatic function.
OBJECTIVE: To evaluate neurodevelopmental status as well as endocrine and exocrine pancreatic function in children who have undergone subtotal pancreatectomy for hypoglycemia due to congenital hyperinsulinism. PATIENTS AND METHODS: Out of 15 identified patients, eight children (mean age 12.7 +/- 0.8 yr) participated in detailed psychometric testing and studies assessing glucose homeostasis, secretion of proinsulin, insulin, glucagon and C-peptide during a test meal. Additionally, a 24-h fast, glucagon challenge test, 72-h stool collection, and ultrasonography of the pancreatic remnant were performed. RESULTS: Five of the 15 initially identified children had seizure disorders, including two with mental retardation. Diabetes developed in two of 15 children. All eight children investigated in the present study had evidence for attentional control impairment and 50% had subnormal intellectual functioning. Two had symptomatic hypoglycemia during the 24-h fast, while one had an elevated fasting glucose concentration. Four children, including the latter patient, had proinsulin/insulin ratios resembling patients with type 2 diabetes. Exocrine pancreatic function was normal in all eight children. No correlation was found between pancreatic endocrine function and pancreatic remnant size, nor between multiple pre- and postoperative factors (i.e., age at diagnosis and surgery) and neurodevelopmental outcome. CONCLUSION: While severe mental retardation or diabetes occurred infrequently in our patient population compared with previous reports, all of the studied children had subtle anomalies in their cognitive performance tests and the majority had endocrine test results indicative of abnormal insulin secretion and stressed pancreatic beta cells. Although partial pancreatectomy remains the treatment of choice after medical therapy fails, improved therapeutic means are necessary to achieve better clinical outcome.
Journal Article↗
Type 2 diabetes impairs splanchnic uptake of glucose but does not alter intestinal glucose absorption during enteral glucose feeding: additional evidence for a defect in hepatic glucokinase activity.
We have previously reported that splanchnic glucose uptake, hepatic glycogen synthesis, and hepatic glucokinase activity are decreased in people with type 2 diabetes during intravenous glucose infusion. To determine whether these defects are also present during more physiological enteral glucose administration, we studied 11 diabetic and 14 nondiabetic volunteers using a combined organ catheterization-tracer infusion technique. Glucose was infused into the duodenum at a rate of 22 micromol. kg(-1). min(-1) while supplemental glucose was given intravenously to clamp glucose at approximately 10 mmol/l in both groups. Endogenous hormone secretion was inhibited with somatostatin, and insulin was infused to maintain plasma concentrations at approximately 300 pmol/l (i.e., twofold higher than our previous experiments). Total body glucose disappearance, splanchnic, and leg glucose extractions were markedly lower (P < 0.01) in the diabetic subjects than in the nondiabetic subjects. UDP-glucose flux, a measure of glycogen synthesis, was approximately 35% lower (P < 0.02) in the diabetic subjects than in the nondiabetic subjects. This was entirely accounted for by a decrease (P < 0.01) in the contribution of extracellular glucose because the contribution of the indirect pathway to hepatic glycogen synthesis was similar between groups. Neither endogenous and splanchnic glucose productions nor rates of appearance of the intraduodenally infused glucose in the portal vein differed between groups. In summary, both muscle and splanchnic glucose uptake are impaired in type 2 diabetes during enteral glucose administration. The defect in splanchnic glucose uptake appears to be due to decreased uptake of extracellular glucose, implying decreased glucokinase activity. Thus, abnormal hepatic and muscle (but not gut) glucose metabolism are likely to contribute to postprandial hyperglycemia in people with type 2 diabetes.
Absorption↗
Lack of suppression of glucagon contributes to postprandial hyperglycemia in subjects with type 2 diabetes mellitus.
We tested the hypothesis that a lack of suppression of glucagon causes postprandial hyperglycemia in subjects with type 2 diabetes. Nine diabetic subjects ingested 50 g glucose on two occasions. On both occasions, somatostatin was infused at a rate of 4.3 nmol/kg x min, and insulin was infused in a diabetic insulin profile. On one occasion, glucagon was also infused at a rate of 1.25 ng/kg x min to maintain portal glucagon concentrations constant (nonsuppressed study day). On the other occasion, glucagon infusion was delayed by 2 h to create a transient decrease in glucagon (suppressed study day). Glucagon concentrations on the suppressed study day fell to about 70 ng/L during the first 2 h, rising thereafter to approximately 120 ng/L. In contrast, glucagon concentrations on the nonsuppressed study day remained constant at about 120 ng/L throughout. The decrease in glucagon resulted in substantially lower (P < 0.001) glucose concentrations on the suppressed compared with the nonsuppressed study days (9.2+/-0.7 vs. 10.9+/-0.8 mmol/L) and a lower (P < 0.001) rate of release of [14C]glucose from glycogen (labeled by infusing [1-14C]galactose). On the other hand, flux through the hepatic UDP-glucose pool (and, by implication, glycogen synthesis), measured using the acetaminophen glucuronide method, did not differ on the two occasions. We conclude that lack of suppression of glucagon contributes to postprandial hyperglycemia in subjects with type 2 diabetes at least in part by accelerating glycogenolysis. These data suggest that agents that antagonize glucagon action or secretion are likely to be of value in the treatment of patients with type 2 diabetes.
Blood Glucose↗
Effects of type 2 diabetes on the ability of insulin and glucose to regulate splanchnic and muscle glucose metabolism: evidence for a defect in hepatic glucokinase activity.
Insulin-induced stimulation of muscle glucose uptake (MGU) is impaired in people with type 2 diabetes. To determine whether insulin-induced stimulation of splanchnic glucose uptake (SGU) is also impaired, we simultaneously measured leg glucose uptake (LGU) and SGU in 14 nondiabetic subjects and 16 subjects with type 2 diabetes using a combined organ catheterization-tracer infusion technique. Glucose was clamped at approximately 9.3 mmol/l, while insulin concentrations were maintained at approximately 72 pmol/l (low) and approximately 150 pmol/l (high) for 3 h each. Endogenous hormone secretion was inhibited with somatostatin. Total body glucose disappearance was lower (P < 0.01) and glucose production higher (P < 0.01) during both insulin infusions in the diabetic compared with the nondiabetic subjects, indicating insulin resistance. Splanchnic glucose production was higher (P < 0.05) in the diabetic subjects during the low but not the high insulin infusion. SGU was slightly lower in the diabetic than in the nondiabetic subjects during the low insulin infusion and 50-60% lower (P < 0.05) during the high insulin infusion. LGU (P < 0.001), but not SGU, was inversely correlated with the degree of visceral adiposity. The contribution of the indirect pathway to hepatic glycogen synthesis did not differ in the diabetic and nondiabetic subjects. In contrast, both flux through the UDP-glucose pool (P < 0.05) and the contribution of the direct pathway to glycogen synthesis (P < 0.01) were lower in the diabetic than in the nondiabetic subjects, indicating decreased uptake and/or phosphorylation of extracellular glucose. On the other hand, glycogenolysis was equally suppressed in both groups. In summary, type 2 diabetes impairs the ability of insulin to stimulate both MGU and SGU. The defect appears to reside at a proximal (e.g., glucokinase) metabolic step and is not related to the degree of visceral adiposity. These data suggest that impaired hepatic glucose uptake as well as MGU contribute to hyperglycemia in people with type 2 diabetes.
Blood Glucose↗
Severe hypoglycemia as a presenting symptom of carbohydrate-deficient glycoprotein syndrome.
We describe clinical, biochemical, and molecular findings in a 2(1/2)-year-old girl with a phosphomannose isomerase deficiency who presented with severe and persistent hypoglycemia and subsequently developed protein-losing enteropathy, liver disease, and coagulopathy. Six months of therapy with mannose supplementation resulted in clinical improvement and partial correction of biochemical abnormalities.
Child, Preschool↗
Hypoglycemia in infants and children.
Hypoglycemia is more common in the pediatric patient than in adults. This article discusses the many diagnoses that can be associated with hypoglycemia in infancy and childhood. A guide to help practitioners evaluate such patients and suggested treatments for many of these disorders are provided. As genetic diagnosis continues to develop, it is anticipated that the list of specific disorders associated with hypoglycemia in infancy and childhood will increase.
Child↗
Accuracy of pen injectors versus insulin syringes in children with type 1 diabetes.
OBJECTIVE: To compare the accuracy and precision of insulin syringes and pen devices used by children with type 1 diabetes and their parents. RESEARCH DESIGN AND METHODS: There were 48 subjects (32 patients, a parent of an additional 16 patients) instructed to measure out morning insulin doses three times from vials and/or cartridges containing saline mixed with small amounts of [14C]glucose (solution used as regular insulin) and [3H]glucose (solution used as NPH insulin) and to dispense the contents into a scintillation vial. Statistical analysis was used to determine the accuracy and precision of both methods of insulin delivery. RESULTS: The absolute error in measuring out doses of regular insulin < 5 U was greater with insulin syringes compared with pen injection devices (9.9 +/- 2.4 vs. 4.9 +/- 1.6%, respectively). Both were comparable for regular insulin doses > 5 U (3.2 +/- 0.6 vs. 2.2 +/- 0.4% for syringes and pens, respectively). The accuracy in drawing up NPH doses was similar for low and high insulin doses (mean percent error of 7.5 +/- 1.5 vs. 5.6 +/- 1.1%). CONCLUSIONS: Pen devices are more accurate than insulin syringes in measuring out insulin at low insulin doses. The accuracy of insulin syringes improves when higher doses of regular insulin are measured out and becomes comparable to pen devices.
Adolescent↗
Type 1 diabetes mellitus in early childhood: glycemic control and associated risk of hypoglycemic reactions.
OBJECTIVE: To assess the level of glycemic control and to determine whether more normal glycemic control, as measured by glycosylated hemoglobin, leads to frequent hypoglycemic episodes in young patients with type 1 diabetes mellitus. MATERIAL AND METHODS: We undertook a retrospective review of the medical records of 59 children with type 1 diabetes diagnosed at age 9 years or younger, who underwent follow-up at our institution for at least 2 years. For each follow-up, insulin requirements, levels of glycosylated hemoglobin, and frequency of hypoglycemic reactions were analyzed for three age-groups--0 to 2 years, 2 to 5 years, and 5 to 9 years old. RESULTS: The mean glycosylated hemoglobin for the first 2 years after diagnosis of type 1 diabetes was higher in children 0 to 2 years old in comparison with the other age-groups. This increased glycosylated hemoglobin occurred despite increased administration of insulin, expressed in units per kilogram daily, to these children (P < 0.05). Severe hypoglycemic reactions were more common in infants (55%) and children between 2 and 5 years old (45%) than in children from 5 to 9 years old (13%). In all age-groups, the mean glycosylated hemoglobin value closest to a hypoglycemic event and the mean glycosylated hemoglobin value for the 2-year study period were similar but were both less than 8% (the standard established by the Diabetes Control and Complications Trial). Most reactions had no clear cause in the youngest age-group, whereas a specific reason could usually be determined in children 2 to 5 years old. CONCLUSION: Tight glycemic control is achievable in young patients with type 1 diabetes mellitus. Such tight control, however, may lead to an increase in the frequency of severe hypoglycemic reactions in this patient population. Our data support the guideline that children younger than 5 years should have a higher goal for premeal plasma glucose levels.
Age Factors↗
Breast milk: revisited.
Human milk has been shown to be the ideal source of nutrition for most growing infants. Its composition continues to be an active area of investigation. In several studies in preterm and term infants, long-chain polyunsaturated fatty acids were found to improve the maturation of visual evoked potentials. The clinical significance of this finding, however, remains unclear. Nucleotides present in breast milk or added to infant formula seem to enhance the humoral immune response to vaccination. Whether breastfeeding protects susceptible infants from the risk of the development of diabetes mellitus type 1 is still controversial. Breastfeeding by mothers infected with the human immunodeficiency virus is not recommended. Other viruses and pollutants have also been found in breast milk. The importance of these in the long-term health of children remains to be established.
Acquired Immunodeficiency Syndrome↗
Assessment of hepatic sensitivity to glucagon in NIDDM: use as a tool to estimate the contribution of the indirect pathway to nocturnal glycogen synthesis.
NIDDM is associated with excessive rates of endogenous glucose production in both the postabsorptive and postprandial states. To determine whether this is due to an intrinsic increase in hepatic sensitivity to glucagon, 9 NIDDM and 10 nondiabetic subjects were studied on three occasions. On each occasion, glycogen was labeled the evening before the study with subjects ingesting meals containing [6-3H]galactose. Beginning at 6:00 A.M. on the following morning, somatostatin was infused to inhibit endogenous hormone secretion. Insulin concentrations were maintained constant at basal levels (defined as that necessary to keep glucose at approximately 5 mmol/l) in each individual. On one occasion, glucagon was infused at a rate of 0.65 ng x kg(-1) x min(-1) throughout the experiment, resulting in glucagon concentrations of approximately 130 pg/ml and a slow but comparable fall in endogenous glucose production with time in both groups. On the other two occasions, the glucagon infusion was increased at 10:00 A.M. to either 1.5 or 3.0 ng x kg(-1) x min(-1), resulting in an increase in glucagon concentrations to approximately 180 and 310 pg/ml, respectively. The increment in endogenous glucose production (i.e., area above basal) did not differ in diabetic and nondiabetic subjects during either the 1.5 ng x kg(-1) x min(-1) (0.75 +/- 0.055 vs. 0.78 +/- 0.048 mmol/kg) or 3.0 ng x kg(-1) x min(-1) (1.06 +/- 0.066 vs. 1.10 +/- 0.073 mmol/kg) glucagon infusions. In contrast, the amount of [6-3H]glucose released from glycogen was lower (P < 0.05) in the diabetic than nondiabetic subjects during both glucagon infusions. The specific activity of glycogen, calculated as the integrated release of [6-3H]glucose divided by the integrated release of unlabeled glucose, was lower (P < 0.05) in diabetic subjects than in nondiabetic subjects during both the 1.5 ng x kg(-1) x min(-1) (19.0 +/- 3.9 vs. 41.4 +/- 5.7 dpm/micromol) and 3.0 ng x kg(-1) x min(-1) (19.1 +/- 3.1 vs. 36.5 +/- 7.2 dpm/micromol) glucagon infusions, implying that a greater portion of the glucose released from glycogen was derived from the indirect pathway. We concluded that although NIDDM is not associated with an intrinsic alteration in hepatic sensitivity to glucagon, it does alter the relative contributions of the direct and indirect pathways to nocturnal glycogen synthesis.
Blood Glucose↗
Acetaminophen glucuronidation accurately reflects gluconeogenesis in fasted dogs.
To assess whether acetaminophen glucuronide accurately reflects uridyl diphosphate-glucose (UDP-glucose) derived from gluconeogenesis during fasting, three mongrel dogs received infusions of [U-14C]lactate, [1-13C]galactose, and [6-3H]glucose (after fasting overnight or for 2.5 days). After initiation of the isotopes (3 h), acetaminophen was given, and the urinary acetaminophen glucuronide was isolated. The mean plasma [14C]glucose specific activity (SA) was similar to the mean urinary acetaminophen glucuronide SA both after fasting overnight [299 +/- 19 vs. 296 +/- 14 disintegrations.min-1 (dpm).mumol-1, respectively] and after 2.5 days of fasting (511 +/- 8 vs. 562 +/- 32 dpm/mumol, respectively). Mean plasma glucose flux calculated using [6-3H]glucose decreased (P < 0.05) with two additional days of fasting (18.7 +/- 1.2 vs. 13.6 +/- 0.6 mumol.kg-1.min-1), as did intrahepatic (P < 0.05) UDP-glucose flux measured using [1-13C]galactose (8.6 +/- 0.7 vs. 5.5 +/- 0.3 mumol.kg-1.min-1). We conclude that, in fasted dogs, plasma glucose and UDP-glucose, as sampled by acetaminophen, equally reflect gluconeogenesis and appear to come from the same pool of glucose 6-phosphate. In addition, cycling of glucose moieties through UDP-glucose and glycogen decreases with an increased period of fasting.
Acetaminophen↗
An unusual case of the nonketotic hyperglycemic syndrome during childhood.
The nonketotic hyperglycemic syndrome is rare during childhood and may occur as the initial manifestation of insulin-dependent diabetes mellitus or during an episode of gastroenteritis. In this article, we report an unusual case of this syndrome in a female infant who had atypically severe hyperglycemia in association with gastroenteritis. In addition, we provide a review of the literature and summarize the pathophysiologic mechanisms of the nonketotic hyperglycemic syndrome.
Child↗
Hepatic glycogen accurately reflected by acetaminophen glucuronide in dogs refed after fasting.
To validate a method to "biochemically biopsy" the immediate precursor of intrahepatic glycogen [uridyl diphosphate (UDP)-glucose] using acetaminophen and to assess how fasting affects the direct and indirect pathways of glycogen synthesis, dogs were fasted overnight (group 1, n = 5) or for 2.5 days (group 2, n = 5) and then given a 4-h duodenal infusion of unlabeled glucose, [3-3H]glucose, and [U-14C]lactate to label hepatic glycogen via the direct and indirect pathways, respectively, and [1-13C]galactose to measure intrahepatic UDP-glucose flux. After 3 h for equilibration, acetaminophen was given and urine was collected for acetaminophen glucuronide. Multiple liver biopsies were obtained. The mean 3H/14C ratios of glucose derived from glycogen (10.4 +/- 4.1 and 1.1 +/- 0.3 for groups 1 and 2, respectively) and glucose derived from acetaminophen glucuronide (11.5 +/- 4.0 and 1.0 +/- 0.1 for groups 1 and 2, respectively) were similar. Fasting significantly increased UDP-glucose flux, the rate of glycogen synthesis, and the contribution of the indirect pathway. We conclude that, in dogs, 1) no functional hepatic zonation exists with regard to acetaminophen glucuronidation and liver glycogen synthesis and 2) with appropriate choice of isotopic tracers and study design, UDP-glucose flux can accurately reflect rates of hepatic glycogen synthesis.
Acetaminophen↗
Glucose production in glycogen storage disease I is not associated with increased cycling through hepatic glycogen.
Children with glycogen storage disease type I (GSD I) lack the ability to convert glucose 6-phosphate to glucose and yet are able to produce glucose endogenously. To test the hypothesis that the source of this glucose is increased cycling of glucose moieties through hepatic glycogen, six children with GSD I were studied on two occasions during which they received enteral glucose for 6 h at 35 or 50 mumol.kg-1.min-1 along with [6,6-2H2]glucose to measure plasma glucose flux and [1-13C]galactose to label intrahepatic uridyl diphosphate (UDP)-glucose. After 3 h, acetaminophen was given to estimate UDP-glucose flux (reflecting the rate of glycogen synthesis). Mean steady-state plasma glucose concentrations (4.8 +/- 0.2 vs. 5.8 +/- 0.1 mM) and total flux (34.8 +/- 1.7 vs. 47.5 +/- 2.0 mumol.kg-1.min-1) were increased (P < 0.05 or better) on the high-infusion day. Endogenous glucose production was detectable only on the low-infusion day (2.0 +/- 0.5 mumol.kg-1.min-1). UDP-glucose flux was increased (P < 0.05) on the high-infusion day (25.8 +/- 1.6 vs. 34.7 +/- 4.1), ruling out cycling of glucose moieties through glycogen with release of glucose by debrancher enzyme as the source of glucose production.
Blood Glucose↗