RESUMO
BACKGROUND: Although minimally invasive surgery has been accepted for a variety of disorders, laparoscopic resection of colorectal cancer is performed by few. Concern about oncological radicality and long term outcome has limited the adoption of laparoscopic surgery for colorectal cancer. OBJECTIVES: To determine long-term outcome after laparoscopically-assisted versus open surgery for non-metastasised colorectal cancer. SEARCH STRATEGY: The Cochrane library, EMBASE, Pub med and Cancer Lit were searched for published and unpublished randomised controlled trials. SELECTION CRITERIA: Randomised clinical trials comparing laparoscopically-assisted and open surgery for non-metastasised colorectal cancer were included. Studies that did not report any long-term outcomes were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the studies and extracted data. RevMan 4.2 was used for statistical analysis. MAIN RESULTS: Thirty-three randomised clinical trials (RCT) comparing laparoscopically-assisted versus open surgery for colorectal cancer were identified. Twelve of these trials, involving 3346 patients, reported long-term outcome and were included in the current analysis. No significant differences in the occurrence of incisional hernia, reoperations for incisional hernia or reoperations for adhesions were found between laparoscopically assisted and open surgery (2 RCT, 474 pts, 7.9% vs 10.9%;P = 0.32 and 2 RCT, 474 pts, 4.0% vs 2.8%; P = 0.42 and 1 RCT, 391 pts, 1.1% vs 2.5%;P = 0.30, respectively). Rates of recurrence at the site of the primary tumor were similar (colon cancer: 4 RCT, 938 pts, 5.2% vs 5.6%; OR (fixed) 0.84 (95% CI 0.47 to 1.52)(P = 0.57); rectal cancer: 4 RCT, 714 pts, 7.2% vs 7.7%; OR (fixed) 0.81 (95% CI 0.45 to 1.43) (P = 0.46). No differences in the occurrence of port-site/wound recurrences were observed (P=0.16). Similar cancer-related mortality was found after laparoscopic surgery compared to open surgery ( colon cancer: 5 RCT, 1575 pts, 14.6% vs 16.4%; OR (fixed) 0.80 (95% CI 0.61 to 1.06) (P=0.15); rectal cancer: 3 RCT, 578 pts, 9.2% vs 10.0%; OR (fixed) 0.66 (95% CI 0.37 to 1.19) (P=0.16). Four studies were included in the meta-analyses on hazard ratios for tumour recurrence in laparoscopic colorectal cancer surgery. No significant difference in recurrence rate was observed between laparoscopic and open surgery (hazard ratio for tumour recurrence in the laparoscopic group 0.92; 95% CI 0.76-1.13). No significant difference in tumour recurrence between laparoscopic and open surgery for colon cancer was observed (hazard ratio for tumour recurrence in the laparoscopic group 0.86; 95% CI 0.70-1.08). AUTHORS' CONCLUSIONS: Laparoscopic resection of carcinoma of the colon is associated with a long term outcome no different from that of open colectomy. Further studies are required to determine whether the incidence of incisional hernias and adhesions is affected by method of approach. Laparoscopic surgery for cancer of the upper rectum is feasible, but more randomised trials need to be conducted to assess long term outcome.
Assuntos
Neoplasias do Colo/cirurgia , Laparoscopia , Neoplasias Retais/cirurgia , Hérnia Ventral/etiologia , Humanos , Laparoscopia/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Competition between glucose and free fatty acids as metabolic fuels is supported by both in vitro and in vivo data, but whether amino acids can also compete with glucose as a source of energy in vivo remains to be established. To determine the effect of increased availability of an amino acid on whole-body glucose flux and glucose carbon uptake by the human forearm, five groups of overnight-fasted normal subjects were infused with either saline, leucine (at 0.5 or 1.0 mumol X kg-1 X min-1), isoleucine (0.5 mumol X kg-1 X min-1), or threonine (0.5 mumol X kg-1 X min-1). Plasma glucose concentrations and glucose flux decreased similarly in all groups. No significant changes in forearm output of leucine carbon, isoleucine carbon, or threonine were seen during saline infusion. In contrast, during leucine infusion there was a dose-dependent increase (r = .86, P less than .001) in leucine carbon uptake with increased arterial leucine and alpha-ketoisocaproate concentrations. During infusions of isoleucine and threonine, increases (P less than .05) in isoleucine carbon uptake and threonine uptake, respectively, were observed. Glucose uptake by forearm tissues did not change during the saline infusion, but it decreased (P less than .05) in all four groups receiving an amino acid infusion. Changes in leucine carbon uptake were strongly correlated (r = -.76, P less than .001) with changes in glucose uptake. Therefore, amino acids affect glucose uptake in human forearm tissue and presumably compete as oxidative fuels.
Assuntos
Glucose/metabolismo , Isoleucina/farmacologia , Leucina/farmacologia , Treonina/farmacologia , Adulto , Glicemia/metabolismo , Peptídeo C/sangue , Relação Dose-Resposta a Droga , Ácidos Graxos não Esterificados/metabolismo , Feminino , Antebraço , Humanos , Infusões Intravenosas , Insulina/sangue , Leucina/administração & dosagem , MasculinoRESUMO
Recent studies indicate that hydrogen-labeled glucose tracers underestimate glucose turnover in humans under conditions of high flux. The cause of this underestimation is unknown. To determine whether the error is time-, pool-, model-, or insulin-dependent, glucose turnover was measured simultaneously with [6-3H]-, [6,6-2H2]-, and [6-14C]glucose during a 7-h infusion of either insulin (1 mU.kg-1.min-1) or saline. During the insulin infusion, steady-state glucose turnover measured with both [6-3H]glucose (8.0 +/- 0.5 mg.kg-1.min-1) and [6,6-2H2]glucose (7.6 +/- 0.5 mg.kg-1.min-1) was lower (P less than .01) than either the glucose infusion rate required to maintain euglycemia (9.8 +/- 0.7 mg.kg-1.min-1) or glucose turnover determined with [6-14C]glucose and corrected for Cori cycle activity (9.8 +/- 0.7 mg.kg-1.min-1). Consequently "negative" glucose production rates (P less than .01) were obtained with either [6-3H]- or [6,6-2H2]- but not [6-14C]glucose. The difference between turnover estimated with [6-3H]glucose and actual glucose disposal (or 14C glucose flux) did not decrease with time and was not dependent on duration of isotope infusion. During saline infusion, estimates of glucose turnover were similar regardless of the glucose tracer used. High-performance liquid chromatography of the radioactive glucose tracer and plasma revealed the presence of a tritiated nonglucose contaminant. Although the contaminant represented only 1.5% of the radioactivity in the [6-3H]glucose infusate, its clearance was 10-fold less (P less than .001) than that of [6-3H]glucose. This resulted in accumulation in plasma, with the contaminant accounting for 16.6 +/- 2.09 and 10.8 +/- 0.9% of what customarily is assumed to be plasma glucose radioactivity during the insulin or saline infusion, respectively (P less than .01). When corrected for the presence of the contaminant, glucose turnover determined with [6-3H]glucose during insulin infusion (9.5 +/- 0.6 mg.kg-1.min-1) no longer differed from either the glucose infusion rate or that determined with [6-14C]glucose. Therefore, the underestimation of glucose turnover during insulin infusion and negative glucose production rates observed with traditional methods to analyze plasma radioactivity and commercially available tracers is the result of an artifactual increase in [6-3H]glucose specific activity. The etiology of the underestimation of glucose turnover with [6,6-2H2]glucose remains to be determined.
Assuntos
Glucose/metabolismo , Insulina/sangue , Adulto , Glicemia/análise , Radioisótopos de Carbono , Cromatografia Líquida de Alta Pressão , Deutério , Feminino , Humanos , Masculino , TrítioRESUMO
To determine the role insulin resistance may play in the catabolic effect of high-dose prednisone therapy, healthy volunteers were studied on four occasions with the hormone-clamp technique at two insulin infusion rates. Subjects were studied after 5 days of prednisone (60 mg/day) or no steroid treatment and were infused with somatostatin, glucagon, growth hormone, [3H]glucose, [14C]leucine, and insulin (0.1 or 0.2 mU.kg-1.min-1). At each rate of insulin infusion, the rate of leucine oxidation was increased (P less than .001) after steroid treatment. Leucine flux, an indicator of whole-body proteolysis, was similar in the presence or absence of steroid treatment (2.26 +/- 0.08 vs. 2.13 +/- 0.04 mumol.kg-1.min-1, respectively) at the lower rate of insulin infusion but was higher during steroid treatment (2.18 +/- 0.06 vs. 1.84 +/- 0.13 mumol.kg-1.min-1) at the 0.2-mU.kg-1.min-1 insulin infusion. Steroid pretreatment had no significant effect on the nonoxidative rates of leucine disappearance. These data provide strong evidence that the protein wasting associated with glucocorticosteroid therapy is in part the result of steroid-induced resistance to the antiproteolytic effect of insulin and an increase in the oxidation (and thus wasting) of one essential amino acid, leucine.
Assuntos
Resistência à Insulina , Insulina/farmacologia , Leucina/metabolismo , Prednisona/farmacologia , Adulto , Metabolismo Basal , Glucagon/farmacologia , Glucose/metabolismo , Hormônio do Crescimento/farmacologia , Humanos , Sistemas de Infusão de Insulina , Cinética , Modelos Teóricos , Oxirredução , Valores de Referência , Somatostatina/farmacologiaRESUMO
To determine the effects of acute metabolic acidosis and alkalosis on leucine metabolism in vivo, mongrel dogs were infused with [1-14C]leucine for 8 h, along with NaCl, HCI, or NaHCO3 over the last 4 h. Arterial pH did not change from the basal value during NaCl infusion but decreased (P less than .01) and increased (P less than .01) during HCl and NaHCO3 infusions, respectively. Total leucine carbon entry did not change from the basal value during saline infusion but increased (P less than .01) with acidosis and decreased (P less than .05) with alkalosis. Compared with saline controls, acidosis increased (P less than .01) leucine oxidation. During alkalosis decreased (P less than .01) leucine oxidation. During acidosis, total plasma essential and nonessential amino acid concentrations increased (P less than .05), whereas during alkalosis, total plasma essential and nonessential amino acid concentrations decreased (P less than .05). These studies suggest that acute alterations in arterial pH may affect the regulation of protein metabolism in vivo and must be considered in the interpretation of results from experiments in which alterations of acid-base homeostasis may have occurred.
Assuntos
Acidose/metabolismo , Alcalose/metabolismo , Leucina/metabolismo , Ácido 3-Hidroxibutírico , Acetoacetatos/sangue , Acidose/sangue , Acidose/induzido quimicamente , Alcalose/sangue , Alcalose/induzido quimicamente , Aminoácidos/sangue , Animais , Bicarbonatos , Gasometria , Glicemia/análise , Estado de Consciência , Cães , Ácidos Graxos não Esterificados/sangue , Glucagon/sangue , Ácido Clorídrico , Concentração de Íons de Hidrogênio , Hidroxibutiratos/sangue , Infusões Intra-Arteriais , Insulina/sangue , Cetoácidos/sangue , Leucina/sangue , Oxirredução , Piruvatos/sangue , Sódio , Bicarbonato de Sódio , Cloreto de Sódio/farmacologiaRESUMO
It is well established that patients with non-insulin-dependent diabetes mellitus (NIDDM) are resistant to insulin. However, the contribution of hepatic and extrahepatic tissues to insulin resistance remains controversial. The uncertainty may be at least in part due to errors introduced by the unknowing use in previous studies of impure isotopes to measure glucose turnover. To determine hepatic and extrahepatic responses to insulin in the absence of these errors, steady-state glucose turnover was measured simultaneously with [6-3H]- and [6-14C]glucose during sequential 5- and 4-h infusions of insulin at rates of 0.4 and 10 mU.kg-1.min-1 in diabetic and nondiabetic subjects. At low insulin concentrations, [6-3H]- and [6-14C]glucose gave similar estimates of glucose turnover. Hepatic glucose release was equal to but not below zero in the nondiabetic subjects, but persistent glucose release (P less than 0.001) and decreased glucose uptake (P less than 0.001) was observed in the diabetic patients. At high insulin concentrations, both isotopes underestimated glucose turnover during the 1st h after initiation of the high-dose insulin infusion. More time (P less than 0.05) was required to reachieve steady state in NIDDM than nondiabetic subjects. At steady state, [6-3H]- but not [6-14C]glucose systematically underestimated (P less than 0.05) glucose turnover in both groups due to the presence of a tritiated nonglucose contaminant. The percentage of radioactivity in plasma due to tritiated contaminants was linearly related to turnover.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Diabetes Mellitus Tipo 2/tratamento farmacológico , Insulina/uso terapêutico , Fígado/efeitos dos fármacos , Adulto , Glicemia/análise , Peptídeo C/sangue , Radioisótopos de Carbono , Cromatografia Líquida de Alta Pressão , Feminino , Glucose/metabolismo , Glucose/farmacocinética , Humanos , Bombas de Infusão , Insulina/sangue , Insulina/farmacologia , Resistência à Insulina/fisiologia , Fígado/fisiologia , Masculino , Pessoa de Meia-Idade , TrítioRESUMO
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.
Assuntos
Ritmo Circadiano , Diabetes Mellitus Tipo 2/metabolismo , Glucagon/biossíntese , Glucagon/farmacologia , Fígado/efeitos dos fármacos , Glicemia/metabolismo , Peptídeo C/sangue , Ácidos Graxos não Esterificados/sangue , Feminino , Glucagon/sangue , Glucose/biossíntese , Glucose/metabolismo , Hormônio do Crescimento Humano/sangue , Humanos , Insulina/sangue , Cinética , Ácido Láctico/sangue , Fígado/metabolismo , Masculino , Pessoa de Meia-IdadeRESUMO
Type A insulin resistance, associated with acanthosis nigricans and menstrual irregularity, has been ascribed to a decreased concentration of insulin receptors. We now report four affected females from one family, a mother and three daughters (including identical twins) who appear to have the type A syndrome. Two of the kindred had no apparent ovarian dysfunction, while the other two had hyperprolactinemia without other findings of polycystic ovary disease, suggesting a genetic disease with variable penetrance. All had normal erythrocyte and monocyte insulin binding. Insulin dose-response studies to assess glucose metabolism and insulin sensitivity were performed in the affected twins. The dose response to insulin was shifted to the right with a decrease in maximal response. These results are consistent with a postbinding defect in insulin action in these patients.
Assuntos
Acantose Nigricans/genética , Acantose Nigricans/metabolismo , Adolescente , Adulto , Glicemia/análise , Doenças em Gêmeos , Feminino , Teste de Tolerância a Glucose , Humanos , Hiperprolactinemia/genética , Insulina/sangue , Insulina/metabolismo , Masculino , LinhagemRESUMO
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.
Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Glucose/metabolismo , Mucosa Intestinal/metabolismo , Vísceras/metabolismo , Absorção , Glicemia/metabolismo , Duodeno , Nutrição Enteral , Glucoquinase/metabolismo , Glucose/administração & dosagem , Glucose/farmacologia , Humanos , Injeções , Injeções Intravenosas , Insulina/sangue , Perna (Membro)/irrigação sanguínea , Fígado/metabolismo , Pessoa de Meia-Idade , Veia Porta , Valores de Referência , Difosfato de Uridina/metabolismo , Uridina Difosfato Ácido Glucurônico/urinaRESUMO
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.
Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Glucose/fisiologia , Insulina/fisiologia , Músculos/metabolismo , Vísceras/metabolismo , Glicemia/análise , Diabetes Mellitus Tipo 2/enzimologia , Diabetes Mellitus Tipo 2/metabolismo , Glucagon/biossíntese , Glucagon/sangue , Glucoquinase/metabolismo , Glucose/biossíntese , Glucose/metabolismo , Glucose/farmacologia , Hormônio do Crescimento Humano/sangue , Humanos , Insulina/sangue , Perna (Membro)/irrigação sanguínea , Fígado/enzimologia , Fígado/metabolismo , Pessoa de Meia-Idade , Ácido Palmítico/sangue , Valores de Referência , Difosfato de Uridina/metabolismoRESUMO
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.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Injeções Subcutâneas/instrumentação , Insulina/administração & dosagem , Seringas , Adolescente , Radioisótopos de Carbono , Criança , Glucose/metabolismo , Humanos , Hipoglicemiantes/uso terapêutico , Injeções Subcutâneas/métodos , Insulina/uso terapêutico , Reprodutibilidade dos Testes , TrítioRESUMO
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.
Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/fisiopatologia , Glucagon/fisiologia , Hiperglicemia/fisiopatologia , Insulina/metabolismo , Período Pós-Prandial , Glicemia/efeitos dos fármacos , Peptídeo C/sangue , Peptídeo C/metabolismo , Diabetes Mellitus Tipo 2/sangue , Feminino , Galactose/metabolismo , Glucagon/sangue , Glucagon/farmacologia , Glicogênio/metabolismo , Hormônio do Crescimento Humano/sangue , Humanos , Hiperglicemia/sangue , Infusões Intravenosas , Insulina/sangue , Insulina/farmacologia , Secreção de Insulina , Masculino , Pessoa de Meia-IdadeRESUMO
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.
Assuntos
Hipoglicemia/etiologia , Criança , Pré-Escolar , Diagnóstico Diferencial , Ácidos Graxos/metabolismo , Gluconeogênese , Doença de Depósito de Glicogênio/complicações , Hormônios/deficiência , Humanos , Hiperinsulinismo/complicações , Hiperinsulinismo/etiologia , Hipoglicemia/diagnóstico , Hipoglicemia/metabolismo , Lactente , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , OxirreduçãoRESUMO
OBJECTIVE: To evaluate whether rehydration of young patients with diabetic ketoacidosis (DKA) by use of a solution that contained 75 mmol/L of sodium would be associated with a decline in serum sodium concentrations. DESIGN: We retrospectively studied 18 episodes of moderate to severe DKA (mean plasma bicarbonate concentration of 7.8 +/- 0.9 mmol/L) in 17 patients younger than 18 years of age who had been examined at the Mayo Clinic between 1986 and 1990. MATERIAL AND METHODS: All patients had received an initial fluid bolus (about 20 mL/kg) of 0.9% saline or Ringer's lactate (or both), followed by rehydration with solutions that contained 75 mmol/L of sodium at rates of approximately 3,000 mL/m2 per day. Mean corrected and uncorrected serum sodium concentrations and effective serum osmolality (before and after administration of the fluid bolus and at 6 and 12 hours into treatment) were compared by use of the paired Student t test. RESULTS: After 12 hours of therapy, we found a significant increase in the mean uncorrected serum sodium level from 135.1 +/- 0.9 mmol/L to 138.1 +/- 0.7 mmol/L (P < 0.05), whereas the mean corrected serum sodium value declined slightly from 143.1 +/- 1.1 mmol/L to 140.4 +/- 0.7 mmol/L (statistically not significant). Serum osmolality based on uncorrected serum sodium concentrations decreased at a rate of 2.6 mmol/kg per hour during the first 6 hours of treatment and remained stable thereafter. CONCLUSION: In 18 episodes of DKA in young patients, rehydration with fluids that contained 75 mmol/L of sodium at rates of approximately 3,000 mL/m2 per day after administration of a fluid bolus of 0.9% saline or Ringer's lactate (or both) was not associated with a decline in the uncorrected serum sodium concentration.
Assuntos
Cetoacidose Diabética/sangue , Cetoacidose Diabética/terapia , Hidratação , Soluções para Reidratação/administração & dosagem , Sódio/administração & dosagem , Sódio/sangue , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Concentração Osmolar , Estudos Retrospectivos , Sódio/análiseRESUMO
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.
Assuntos
Coma Hiperglicêmico Hiperosmolar não Cetótico , Criança , Pré-Escolar , Desidratação/etiologia , Desidratação/terapia , Feminino , Hidratação/efeitos adversos , Gastroenterite/complicações , Gastroenterite/terapia , Gastroenterite/virologia , Humanos , Coma Hiperglicêmico Hiperosmolar não Cetótico/etiologia , Lactente , Infecções por Rotavirus/complicações , Infecções por Rotavirus/terapiaRESUMO
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.
Assuntos
Diabetes Mellitus Tipo 1/terapia , Hemoglobinas Glicadas/metabolismo , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Fatores Etários , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/dietoterapia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Feminino , Humanos , Hipoglicemia/sangue , Lactente , Masculino , Estudos RetrospectivosRESUMO
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.
Assuntos
Aleitamento Materno , Leite Humano , Síndrome da Imunodeficiência Adquirida/prevenção & controle , Síndrome da Imunodeficiência Adquirida/transmissão , Diabetes Mellitus/metabolismo , Humanos , Leite Humano/químicaRESUMO
The medical emergency of diabetic ketoacidosis is a particular problem for children with insulin-dependent diabetes because it is frequently associated with their initial presentation. Subsequent episodes can be prevented with proper use of personal glucose monitoring. The pathophysiology and diagnosis of diabetic ketoacidosis are reviewed, and a framework for the management of this complication in children is provided.