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Biomedical subjects

M J Castillo

Publications and source records attributed to M J Castillo.

At least 37 records · Page 2Linked to original sources
PubMed1996

The degree/rapidity of the metabolic deterioration following interruption of a continuous subcutaneous insulin infusion is influenced by the prevailing blood glucose Level.

This study aims at investigating the influence of the prevailing blood glucose level on the metabolic deterioration that follows a nocturnal interruption of a continuous sc insulin infusion (CSII). Fifteen CSII-treated, C-peptide negative, diabetic patients have been studied CSII was interrupted from 2300 h to 0500 h. Blood was collected hourly from 2200 h to 0600 h. According to blood glucose (BG) levels at 2300 h, patients were classified as hypoglycemic (BG between 1.5 and 2.5 mmol/L, n = 5), normoglycemic (BG between 4.0 and 8.0 mmol/L, n = 5), or hyperglycemic (BG between 9.0 and 15.0 mmol/L, n = 5). At 2300 h, BG (mean +/- SEM) was 1.9 +/- 0.1, 6.2 +/- 0.7 and 11.2 +/- 1.0 mmol/L, respectively. After 6 h of CSII interruption, BG increased to 13.5 +/- 1.3, 14.1 +/- 1.2, and 19.4 +/- 1.2 mmol/L, respectively. At 2300 h, plasma 3-OH-butyrate levels were similar in the three groups (around 150 micromol/L). At 0500 h, significantly higher values were obtained for hyperglycemic (1460 +/- 127 micromol/L) than for normoglycemic (868 +/- 150 micromol/L) or hypoglycemic (837 +/- 80 micromol/L) patients. Enhanced lipolysis in initially hyperglycemic patients may contribute to accelerated ketogenesis and metabolic degradation. In conclusion, the metabolic deterioration that follows CSII interruption is influenced by the initial metabolic situation. Hypoglycemic patients deteriorate more rapidly, and hyperglycemic patients suffer a more important degradation. The latter are prone to rapid ketoacidosis if accidental CSII interruption occurs.

3-Hydroxybutyric Acid↗
PubMed1996

Assessment of residual insulin secretion in diabetic patients using the intravenous glucagon stimulatory test: methodological aspects and clinical applications.

Defective insulin secretion plays a crucial role in insulin-dependent (Type 1) and non-insulin-dependent (Type 2) diabetes mellitus as well as in many secondary forms of the disease. Glucagon is a potent stimulus for the islet beta-cell, and intravenous bolus injection of 1 mg glucagon has been widely used to assess endogenous insulin secretion for clinical or research purposes. Plasma C-peptide levels (less commonly insulin) are usually measured immediately before and 6 min after glucagon injection. The C-peptide response to glucagon is well-correlated with the beta-cell response to mixed meals or other stimuli commonly used to characterize endogenous insulin secretion (oral or intravenous glucose, standard meals, arginine, etc.) and has the advantage of shorter duration and simple standardization. The glucagon test shows good intra-subject reproducibility, although in diabetic patients it may be influenced by variable prevailing blood glucose levels. Several applications of the glucagon test have been developed. In Type 1 diabetes, the glucagon test has been used to discriminate between patients with and without residual insulin secretion. This can be especially important during the first few months, or even years, following initiation of insulin therapy when attempts to stop the immunological destruction of the beta-cell are made. Assessment of endogenous insulin secretion is also important after pancreas or islet transplantation. In patients with Type 2 diabetes mellitus, in which residual endogenous insulin secretion is common, characterization of the disease may help in the choice of therapy for the individual patient (insulin, sulphonylureas or combined therapy). Thus, the glucagon test is a simple, reliable and useful tool for clinical evaluation of diabetes mellitus.

Arginine↗
PubMed1996

Exhaustion of blood glucose response and enhancement of insulin response after repeated glucagon injections in type-2 diabetes: potentiation by progressive hyperglycemia.

AIMS: To investigate the hyperglycemic and insulinemic response to repeated glucagon injections in Type-2 (non-insulin-dependent) diabetic patients. METHODS: In overnight fasted Type-2 diabetic patients, three i.v. glucagon (1 mg) injections were given as a bolus at two-hour intervals. In the hour preceding each glucagon injection, 6 patients received saline and they were tested at near-baseline blood glucose levels, while 8 patients received a glucose-controlled glucose infusion and they were tested at increasing blood glucose levels (7.5 +/- 0.2, 12.9 +/- 0.5 and 18.7 +/- 0.7 mmol/l). Blood samples were collected at 0, 3, 5, 10, 15, 30 and 60 min after each glucagon injection. RESULTS: In the patients tested at near-baseline blood glucose levels, the blood glucose rise induced by glucagon was smaller after repeated injections. By contrast, the B-cell response to glucagon was well preserved. In the patients tested at increasing blood glucose levels, the blood glucose response to glucagon was abolished after repeated injections. By contrast, the B-cell response was significantly potentiated. The respective areas under the curve of plasma insulin levels in response to glucagon were 563 +/- 72, 1047 +/- 154 and 1844 +/- 305 m U x 30 min/l (p < 0.001). CONCLUSION: In Type-2 (non-insulin-dependent) diabetic patients, repeated glucagon injections, even when administered in a short (4 h) period of time, do not exhaust the B-cell. Endogenous insulin secretion is even potentiated at increasing blood glucose levels. By contrast, the hyperglycemic response to glucagon is significantly abolished, particularly at high blood glucose levels.

Aged↗
PubMed1995

TAP polymorphism in patients with Behçet's disease.

OBJECTIVE: To determine if susceptibility to Behçet's disease (BD) is associated with polymorphism of HLA-DRB1, HLA-DQB1, DQB1, and TAP1 and TAP2 genes. METHODS: Fifty eight Spanish BD patients and 116 ethnically matched unrelated healthy subjects were typed at the HLA-DRB1 and HLA-DQB1 loci using polymerase chain reaction/sequence specific oligotyping (PCR/SSO). TAP1 and TAP2 alleles were assigned using amplification refractory mutation system-PCR. RESULTS: TAP1C was absent in BD patients, but was found in 12.1% of control subjects (pcorr < 0.05; relative risk = 0.06). Additionally, a linkage disequilibrium between HLA-DQB1*0501 and TAP2B was observed in BD patients (delta = 0.095, pcorr < 0.02), but not in the control group (delta = -0.0031, p > 0.05). CONCLUSIONS: The complete absence of TAP1C alleles in BD patients may indicate that TAP1 polymorphism is not without some significance in the development of BD. Furthermore, the existence of a linkage disequilibrium between HLA-DQB1*0501 and TAP2B in our patients suggests that the gene conferring susceptibility for BD is inherited as an extended haplotype in the population studied.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1995

Modified glucagon test allowing simultaneous estimation of insulin secretion and insulin sensitivity: application to obesity, insulin-dependent diabetes mellitus, and noninsulin-dependent diabetes mellitus.

The aim of this study was to describe an adaptation of the glucagon test allowing the simultaneous characterization of insulin secretion and sensitivity. A glucagon test (1 mg/m2) was performed in healthy subjects (n = 11), obese patients (n = 5), insulin-dependent diabetics (n = 9), nonobese noninsulin-dependent diabetics (n = 7), and overweight noninsulin-dependent diabetics (n = 8). Previously, they had been connected to the Biostator, modified for continuous blood collection. Endogenous insulin secretion induced by glucagon was derived from integrated C-peptide concentrations. An index of insulin sensitivity was obtained by dividing the rate of decrease in blood glucose by the total amount of insulin entering the circulation (secreted+infused by the Biostator). The indices of insulin sensitivity obtained in the above groups of subjects were, respectively, 0.064 +/- 0.006, 0.030 +/- 0.006, 0.037 +/- 0.007, 0.021 +/- 0.006, and 0.016 +/- 0.002 mmol/L.U.min (P < 0.001). The estimated insulin secretion values in the 20 min following glucagon injection were, respectively, 0.38 +/- 0.05, 0.65 +/- 0.08, 0.05 +/- 0.01, 0.26 +/- 0.15, and 0.30 +/- 0.07 U (P < 0.001). The insulin sensitivity index obtained from this test correlated with the glucose MCR obtained from a euglycemic glucose clamp (r = 0.816; P < 0.001; n = 12). C-Peptide levels after glucagon administration were also significantly correlated with the estimated endogenous insulin secretion (r = 0.808; P < 0.001; n = 30). This adaptation of the classical glucagon test is an efficient and simple method to simultaneously evaluate insulin secretion and insulin sensitivity.

Adult↗
PubMed1995

Amylin/islet amyloid polypeptide: biochemistry, physiology, patho-physiology.

Amylin is a 37 amino-acid peptide mainly produced by the islet beta-cell. Aggregation of amylin is partly responsible for amyloid formation. Amyloid deposits occur both extracellularly and intracellularly and may contribute to beta-cell degeneration. Amylin is packed in beta-cell granules and cosecreted with insulin in response to the same stimuli but, unlike other beta-cell products, it is produced from specific a gene on chromosome 12. Basal, plasma amylin concentrations are around 5 pM, and increase fourfold after meals or glucose. Higher levels are found in cases of insulin resistance, obesity, gestational diabetes and in some patients with NIDDM. Low or absent levels are found in insulin-dependent diabetic patients. There are similarities between amylin and non beta-cell peptides such as calcitonin gene related peptides (CGRP). They may bind to the same receptor, determine similar post-receptor phenomena and qualitatively similar actions but with different degree of potency. The actions of amylin are multiple and mostly exerted in the regulation of fuel metabolism. In muscle, amylin opposes glycogen synthesis, activates glycogenolysis and glycolysis (increasing lactate production). Consequently, amylin increases lactate output by muscle and increases the plasma lactate concentration. In fasting conditions, this lactate may serve as a gluconeogenic substrate for the liver, contributing to replenish depleted glycogen stores and to increase glucose production. In non-fasting conditions, lactate can be transformed by liver in triglycerides. It is not clear at present whether amylin actions on the liver are direct or mediated by changes in circulating metabolites. A probably indirect effect of amylin in muscle is to decrease insulin- (or glucose)-induced glucose uptake, which may contribute to insulin resistance. Other actions include inhibition of glucose-stimulated insulin secretion and, in general, actions mimicking CGRP effects. Some of these actions are seen at supraphysiological concentrations. The physiopathological consequences of amylin deficiency, or excess are under active by investigated.

Amino Acid Sequence↗
PubMed1995

Glucose metabolism in obese subjects: lessons from OGTT, IVGTT and clamp studies.

Impaired glucose tolerance and overt diabetes are more frequent in presence than in absence of obesity. In obese subjects, glucose tolerance can be maintained within the normal range by compensating for insulin resistance by peripheral hyperinsulinism, the latter resulting from both increased insulin secretion and reduced insulin clearance. Impaired glucose tolerance is observed when insulin resistance is associated to impaired first-phase insulin response, which results in a significant increase in plasma glucose levels and a late insulin hyperresponsiveness. Both hyperinsulinaemia and hyperglycaemia are then able to overcome peripheral insulin resistance and impaired glucose disposal. When a more marked defect in insulin secretion is present, hyperglycaemia progresses, probably due to an additional participation of impaired suppression of hepatic glucose output. Overt diabetes then occurs with persistent post-absorptive hyperglycaemia. All these abnormalities can be reversed after a marked weight loss and recovery of ideal body weight, arguing for acquired rather than inherited metabolic defects in presence of morbid obesity. If a sufficient weight reduction can not be obtained, pharmacological approaches may be considered to improve insulin resistance of obese subjects, especially those with impaired glucose tolerance or overt diabetes.

Blood Glucose↗
PubMed1995

Retinopathy, but not neuropathy, is influenced by the level of residual endogenous insulin secretion in type 2 diabetes.

The files of 132 patients with Type 2 diabetes were retrospectively studied to characterize the influence of metabolic control and residual insulin secretion on neuropathy and retinopathy, the two most frequent degenerative diabetic complications. Patients were classified according to their metabolic control (mean HbA1C either < or > or = 8%; reference values: 3-6%) and residual endogenous insulin secretion (fasting plasma C-peptide levels either < or > or = 0.600 nmol/l). Neuropathy was more frequent in patients with poor metabolic control (32/64 = 50%) than in those adequately controlled (17/68 = 25%; p < 0.005). In both subgroups, the level of endogenous insulin secretion did not influence the prevalence of neuropathy. Retinopathy was less effected than neuropathy by the degree of metabolic control (37.5% in the subgroup with HbA1C > or = 8% v.s. 25% in the subgroup with HbA1C < 8%; p < 0.10), but was influenced by residual insulin secretion. Indeed, in patients with inadequate metabolic control, the prevalence of retinopathy was significantly increased in those with higher endogenous insulin secretion (51.4 versus 20.6%, p < 0.02) and thus probably higher insulin resistance. Furthermore, higher systolic arterial blood pressure was observed in the subgroups with a higher prevalence of retinopathy. Such conclusions were confirmed using multivariate analysis. Thus, in Type 2 diabetes, neuropathy is essentially affected by the degree of metabolic control, whereas retinopathy is also influenced by the level of residual endogenous insulin secretion and the presence of systolic hypertension.

Adult↗
PubMed1995

[How to explore insulin sensitivity in man?].

The two most widely used methods for studying insulin sensitivity in man are the euglycaemic hyperinsulinaemic clamp and the intravenous glucose tolerance test with minimal model assessment. The glucose clamp is the reference method, well validated and easy to interpret, which allows various extensions to the basic experimental procedure in order to obtain more valuable information on the specific effects of insulin on the various aspects of glucose metabolism. However, it is time-consuming and labour-intensive. In contrast, the intravenous glucose tolerance test is easier to perform, but its interpretation is much more difficult and requires a modeling approach called the "minimal model". If the intravenous glucose tolerance test probably represents a good screening test, mainly on a population basis, the glucose clamp still remains the gold standard method to study insulin sensitivity in man.

Female↗
PubMed1995

Deterioration of the plasma lipid profile during hospitalization of aged non-insulin-dependent diabetic patients. Comparison with non-diabetic control patients.

This study aimed at investigating the changes occurring in the plasma lipid profile of patients with non-insulin-dependent diabetes mellitus (NIDDM) hospitalized for treatment of intercurrent diseases. Twenty-nine non-insulin requiring NIDDM patients (13 men, 16 women; mean age: 67 +/- 2 yrs) and 26 adequately matched patients (12 men, 14 women; mean age: 71 +/- 2 yrs) have been prospectively studied. They were all hospitalized for treatment of various diseases. Diabetic and non-diabetic patients received similar treatment except for intensive insulin therapy in the former group. On admission, diabetic subjects had significantly higher plasma levels of triglycerides and lower levels of HDL cholesterol; during hospitalization, LDL, HDL cholesterol and apo A1 levels increased significantly. In the non-diabetic group, hospitalization and treatment induced significant increases in triglycerides, LDL cholesterol and apo B levels. In conclusion, although insulin treatment during hospitalization of non-insulin requiring NIDDM patients does not fully reverse the abnormal lipid profile, it may help to prevent its further deterioration, particularly by increasing HDL cholesterol levels and hence by decreasing the LDL/HDL cholesterol ratio.

Age Factors↗
PubMed1994

Measurement of apolipoproteins B and A by radial immunodiffusion: methodological assessment and clinical applications.

The clinical evaluation of apolipoproteins is of interest in order to characterize the risk profile for ischemic heart disease both in normolipidemic and hyperlipidemic subjects. In the non-specialized and/or small practice clinical laboratory, the measurement of some apolipoproteins can be undertaken by simple methods of immunological analysis, among which radial immunodiffusion can be of interest due to its simplicity of use and because it does not require specific equipment. In this work several methodological questions concerning the measurement of plasma apolipoproteins B and A by radial immunodiffusion have been addressed; the results show that this method is particularly reliable for the apo B assay. Regression analysis between values obtained with radial immunodiffusion and radioimmunoassay was r = 0.972 for apo B and r = 0.782 for apo A. The recovery rate was above 90% for both apolipoproteins (93.8% for apo B and 99.5% for apo A). The inter and intraassay coefficients of variation were below 5%, and the detection limits were estimated as 9.6 mg/dl for apo A and 6.9 mg/dl for apo B. Neither the ingestion of a standard breakfast (500 Cal, 17 g fat, 120 mg cholesterol) 2 h prior to testing nor freezing the sample significantly affected the measurement of apolipoproteins B and A. Mean plasma concentrations of both apolipoproteins measured by radial immunodiffusion in normo and hyperlipidemic subjects are also presented.

Adult↗
PubMed1994

Metabolic clearance rate of insulin in type 2 diabetic patients treated with combined insulin and sulfonylurea therapy.

The metabolic clearance rate of insulin (MCRI) in 10 non-obese type 2 diabetic patients treated with either insulin alone or combined insulin plus sulfonylurea therapy is investigated. A classical 2-hour euglycaemic hyperinsulinaemic glucose clamp using the artificial pancreas was performed in a randomized order after two 6-week periods of treatment: either with subcutaneous injections of insulin alone or with insulin plus oral administration of the sulfonylurea compound glipizide at the dose of 3 x 10 mg/day. The MCRI was calculated knowing the constant insulin infusion rate (0.1 U.kg-1.h-1) and measuring basal and steady-state plasma free insulin and C-peptide levels. When the test was performed at the end of the period of treatment with insulin plus glipizide and 30 min after the ingestion of the last dose of 10 mg glipizide, plasma C-peptide levels were significantly increased and steady-state free insulin levels tended to be slightly higher whereas the metabolic clearance rate of glucose was not affected. The MCRI was significantly reduced by glipizide from 23.3 +/- 2.9 to 18.9 +/- 2.0 ml.kg-1.min-1 p < 0.05. These results demonstrate that the sulfonylurea glipizide decreases the MCRI. This effect may play a role in the hypoglycemic action of sulfonylureas.

Cross-Over Studies↗
PubMed1994

Relationships between metabolic clearance rate of insulin and body mass index in a female population ranging from anorexia nervosa to severe obesity.

Changes in the metabolic clearance rate of insulin (MCRI) have been described in several pathological conditions. Conflicting data suggest that they may be related to either body mass index (BMI) or body composition. This study aimed to investigate the relationship between the MCRI and BMI in an exclusively female population showing a wide range of BMI. For that purpose, hyperinsulinemic normoglycemic glucose clamps were performed in nine anorectic subjects (BMI: 14.5 +/- 0.8 kg/m2), 11 healthy volunteers (BMI: 20.3 +/- 0.5 kg/m2) and 12 obese patients (BMI: 33.0 +/- 0.9 kg/m2). To exclude any influence of the menstrual cycle on the MCRI, five healthy women underwent three tests at different days of the menstrual cycle: menstruation period, late follicular pre-ovulatory phase and luteal phase, in random order. The MCRI, which was quite reproducible in a given subject, was not significantly modified by the menstrual cycle. In the premenopausal female population studied, the mean (+/- s.e.m.) MCRI normalized for body weight (kg) were 35.4 +/- 3.4, 24.7 +/- 1.8 and 14.0 +/- 1.0 ml/kg/min (P < 0.01) for anorectic subjects, healthy volunteers and obese patients, respectively. These differences were maintained when the MCRI was normalized according to corporeal surface (m2) (1018 +/- 75, 859 +/- 67, 638 +/- 40 ml/m2/min, P < 0.01) or lean body mass (kg) (37.1 +/- 3.4, 32.6 +/- 2.7 and 24.1 +/- 0.5 ml/kgLBM/min, P < 0.01), but disappeared when MCRI was expressed per kg of ideal body weight (24.6 +/- 2.2, 24.6 +/- 2.1 and 22.4 +/- 1.4 ml/kgIBW/min, n.s.).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗