RESUMEN
AIM: The prevalence of diabetes mellitus among Malaysians aged ≥ 30 years of age has increased by more than twofold over a 20-year period. This study aimed to determine the current status and to evaluate the diagnostic usefulness of the HbA(1c) cut-off point of 48 mmol/mol (6.5%). METHODS: Using a two-stage stratified sampling design, participants aged ≥ 18 years were recruited from five zones selected to represent Malaysia. An oral glucose tolerance test was performed on all those not known to have diabetes. RESULTS: A total of 4341 subjects were recruited. By World Health Organization criteria, the prevalence of diabetes mellitus was 22.9%; of that percentage, 10.8% was known diabetes and 12.1% was newly diagnosed diabetes. Diabetes was most prevalent amongst Indians (37.9%) and Malays (23.8%). Prevalence of new diabetes mellitus was only 5.5% (95% CI 4.9-6.3) when based on the HbA(1c) diagnostic criteria of 48 mmol/mol (6.5%) and, although the cut-off point was highly specific (98.1%), it was less sensitive (36.7%) compared with 45 mmol/mol (6.3%), which showed the optimal sum of sensitivity (42.5%) and specificity (97.4%) in identifying new diabetes mellitus. CONCLUSION: This study recorded an overall diabetes prevalence of 22.6%, almost a twofold increase from 11.6% reported in 2006. This was likely attributable to the higher prevalence of new diabetes (12.1%) diagnosed following an oral glucose tolerance test. An HbA(1c) of 45 mmol/mol (6.3%) was found to be a better predictive cut-off point for detecting new diabetes in our multi-ethnic population.
Asunto(s)
Diabetes Mellitus/sangre , Diabetes Mellitus/epidemiología , Adulto , China/etnología , Etnicidad , Femenino , Prueba de Tolerancia a la Glucosa , Hemoglobina Glucada/análisis , Humanos , India/etnología , Malasia/epidemiología , Masculino , Persona de Mediana Edad , Curva ROC , Valores de Referencia , Sensibilidad y Especificidad , Organización Mundial de la SaludRESUMEN
Prior to the implementation of Haemophilus influenzae type b vaccination worldwide, H. influenzae has been one of the main causative agents of community acquired pneumonia and meningitis in children. Due to the lack of information on the characteristics of the H. influenzae isolates that have previously been collected in Malaysia, the H. influenzae were assessed of their microbial susceptibility to commonly used antibiotics. Emphasis was made on strains that were resistance to co-trimoxazole (SXT) and their mode of transfer of the antibiotic resistance determinants were examined. A collection of 34 H. influenzae isolates was serotyped and antimicrobial susceptibility tests were performed to 11 antibiotics. To the isolates that were found to be resistant to co-trimoxazole, minimum inhibition concentration (MIC) to SXT was performed using Etest while agar dilution method was used to measure the individual MICs of trimethoprim (TMP) and sulfamethoxazole (SUL). These isolates were also examined for presence of plasmid by PCR and isolation method. Conjugal transfers of SXT-resistant genes to SXT-susceptible hosts were performed to determine their rate of transfer. Result showed that 20.6% of the total number of isolates was serotype B while the remaining was non-typeable. Antimicrobial susceptibility profile of all the isolates revealed that 58.8% was resistant to at least one antibiotic. Majority of these isolates were equally resistant to ampicillin and tetracycline (29.4% each), followed by resistance to SXT (26.5%). From nine isolates that were found to be SXT-resistant, five contained plasmid/s. Conjugal transfer experiment showed that these five isolates with plasmid transferred SXT-resistance determinants at a higher frequency than those without. From these observations, it is postulated that plasmid is not involved in the transfer of SXT-resistance genes but presence of plasmid facilitates their transfer. The information obtained from this study provides some basic knowledge on the antimicrobial susceptibility pattern of the H. influenzae isolates and their mode of transfer of SXT-resistance genes.
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Antibacterianos/farmacología , Infecciones por Haemophilus/microbiología , Haemophilus influenzae/efectos de los fármacos , Haemophilus influenzae/genética , Combinación Trimetoprim y Sulfametoxazol/farmacología , Ampicilina/farmacología , Niño , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Infecciones Comunitarias Adquiridas/microbiología , ADN Bacteriano/genética , Farmacorresistencia Bacteriana Múltiple , Infecciones por Haemophilus/tratamiento farmacológico , Haemophilus influenzae/inmunología , Haemophilus influenzae/aislamiento & purificación , Humanos , Malasia , Pruebas de Sensibilidad Microbiana , Fenotipo , Plásmidos/genética , Neumonía Bacteriana/tratamiento farmacológico , Neumonía Bacteriana/microbiología , Serotipificación , Tetraciclina/farmacologíaRESUMEN
AIMS: Cardiovascular disease is the foremost cause of mortality in Malaysia but little is known about the prevalence of the metabolic syndrome and its associations with other known cardiovascular risk markers. We undertook a population-based study to examine these. METHODS: For the study, 4341 subjects were selected using a multistage stratified sampling method. Subjects were interviewed for personal and past medical history. Biomedical markers and anthropometric indices were measured. The metabolic syndrome was defined using the harmonized criteria. The associations between the metabolic syndrome and cardiovascular risk markers, including high-sensitivity C-reactive protein, microalbuminuria and HbA(1c) were examined. RESULTS: The prevalence of the metabolic syndrome was 42.5%. Subjects with the metabolic syndrome are significantly more likely to have higher BMI (> 25 kg/m(2)), HbA(1c) [≥ 42 mmol/mol (6.0%)], LDL (≥ 2.6 mmol/l), elevated albumin:creatinine ratio (> 2.5 µg/mmol creatinine for men, 3.5 µg/mmol creatinine for women) and high-sensitivity C-reactive protein (> 3 mg/l); odds ratio 5.48, 6.14, 1.44, 3.68 and 1.84, respectively, P < 0.001. The presence of an elevated albumin:creatinine ratio and high-sensitivity C-reactive protein are strong predictors for the presence of a higher number of positive criteria of the metabolic syndrome. HbA(1c) > 48 mmol/mol (6.5%) is associated with increased relative risk of elevated albumin:creatinine ratio, high-sensitivity C-reactive protein and LDL (relative risk 3.10, 2.46 and 1.65 respectively, P < 0.001). CONCLUSIONS: We confirmed the high prevalence of the metabolic syndrome in Malaysia. Our study revealed a strong relationship between risk markers of elevated BMI, HbA(1c), LDL, albumin:creatinine ratio and high-sensitivity C-reactive protein with the presence of the metabolic syndrome, putting them at a statistically high risk for cardiovascular mortality.
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Proteína C-Reactiva/metabolismo , LDL-Colesterol/sangre , Creatina/sangre , Hemoglobina Glucada/metabolismo , Síndrome Metabólico/sangre , Isquemia Miocárdica/sangre , Adulto , Biomarcadores/sangre , Índice de Masa Corporal , Estudios Transversales , Femenino , Humanos , Malasia/epidemiología , Masculino , Síndrome Metabólico/epidemiología , Persona de Mediana Edad , Isquemia Miocárdica/epidemiología , Isquemia Miocárdica/prevención & control , Valor Predictivo de las Pruebas , Prevalencia , Medición de Riesgo , Factores de RiesgoRESUMEN
Construction of a neovagina is the next step for women with an absent vagina who have failed vaginal dilator therapy. Traditional operative techniques such as skin grafting or intestinal substitution have major disadvantages including prolonged recovery time and significant scarring. Laparoscopic vaginoplasty is performed widely throughout Europe but has not been available in the UK until now. We report on five women who underwent laparoscopic vaginoplasty. Three women underwent a laparoscopic Vecchietti procedure and two underwent a laparoscopic Davydov procedure. Details were recorded on preoperative features, perioperative problems and early postoperative outcome. Laparoscopic vaginoplasty is a safe treatment for vaginal agenesis, and short-term results are encouraging.
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Laparoscopía/métodos , Estructuras Creadas Quirúrgicamente , Vagina/anomalías , Vagina/cirugía , Adolescente , Adulto , Diseño de Equipo , Femenino , Humanos , Tiempo de Internación , Persona de Mediana Edad , Expansión de Tejido/métodos , Resultado del TratamientoRESUMEN
The concentration of plasma sialic acid was estimated using the modified chemical method and the more sensitive enzymatic method in 20 subjects with impaired glucose tolerance and 20 control subjects. The mean sialic acid concentration values of the control subjects and subjects with impaired glucose tolerance using the enzymatic method were 1.747 +/- 0.047 and 2.583 +/- 0.070 mmole/l and 1.753 +/- 0.067 and 2.591 +/- 1.02 mmole/l for the chemical method. The intra-assay coefficient of variation for the control subjects and for the subjects with impaired glucose tolerance were 1.963% and 1.583%, respectively, for the enzymatic assay and 2.728% and 2.431%, respectively, for the chemical assay. The inter-assay coefficient of variation for the control subjects and for the subjects with impaired glucose tolerance were 2.686% and 2.723% for the enzymatic assay, and 3.819% and 3.95% for the chemical assay. Since the values do not differ significantly, the chemical assay is a cost effective method that can be used in large epidemiological studies.
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Técnicas de Química Analítica/métodos , Ensayo de Inmunoadsorción Enzimática/métodos , Ácido Peryódico , Resorcinoles , Ácidos Siálicos/análisis , Técnicas de Química Analítica/economía , Humanos , Malasia , Juego de Reactivos para Diagnóstico , Reproducibilidad de los ResultadosRESUMEN
We examined the prevalence of diabetes among inpatients in our hospital, the relationship of the diagnoses on admission to diabetes, and the frequency of testing for HbA1c as a marker of long-term glycaemic control, proteinuria, and hypercholesterolaemia. In addition, patients with raised laboratory plasma glucose without a know history of diabetes mellitus, were studied to see if these had been further evaluation. The overall prevalence of diabetes in our hospital was 25.% with the highest prevalence found (37.8%) on medical wards. 10.5% of admissions were due directly to diabetes and a further 58.9% of patients were admitted with illness which were significant related to diabetes. Overall testing rates for HbA31c, proteinuria, and hypercholesterolaemia were less than ideal (51.6, 73.4 and 45.% respectively). Less than 50% of patients without previously diagnosed diabetes but with high plasma glucose values had further evaluation for diabetes. In conclusion, this study has detected a high overall prevalence of diabetes among inpatients in an urban Malaysian hospital. Rates of testing for HbA51c, proteinuria, and hypercholesterolaemia, are disappointingly low, as is further evaluation of patients without known diabetes, but with elevated glucose values. More effective measures to improve the delivery of inpatient diabetes care are needed.
Asunto(s)
Diabetes Mellitus , Hipercolesterolemia , Diabetes Mellitus/epidemiología , Hospitales de Enseñanza , Humanos , Prevalencia , ProteinuriaRESUMEN
AIMS: To define the prevalence of dyslipidaemia in young diabetic patients in Peninsular Malaysia and the contributory factors of dyslipidaemia in these subjects. METHODS: This is a cross-sectional study involving 848 young diabetic patients from seven different centres, with representation from the three main ethnic groups. Clinical history and physical examination was done and blood taken for HbA1c, fasting glucose, total cholesterol, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol and triglycerides. RESULTS: The overall lipids were suboptimal, worse in Type 2 diabetes mellitus (DM) patients compared with Type 1 DM patients. Of the Type 2 patients, 73.2% had total cholesterol > 5.20 mmol/l, 90.9% had LDL-cholesterol > 2.60 mmol/l, 52.6% had HDL-cholesterol < 1.15 mmol/l and 27.3% had serum triglycerides > 2.30 mmol/l. There were ethnic differences in the lipid levels with the Malays having the highest total cholesterol (mean 6.19 mmol/l), and the highest LDL-cholesterol (mean 4.16 mmol/l), while the Chinese had the highest HDL-cholesterol (geometric mean 1.24 mmol/l). Ethnicity was an important determinant of total, LDL- and HDL-cholesterol in Type 2 DM, and LDL- and HDL-cholesterol and triglycerides in Type 1 DM. Glycaemic control was an important determinant of total, LDL-cholesterol and triglycerides in both Type 1 and Type 2 DM. Waist-hip ratio (WHR) was an important determinant of HDL-cholesterol and triglycerides in both types of DM. Gender was an important determinant of HDL-cholesterol in Type 2 DM, but not in Type 1 DM. Socioeconomic factors and diabetes care facilities did not have any effect on the dyslipidaemia. CONCLUSIONS: The prevalence of dyslipidaemia was high especially in Type 2 DM patients. Ethnicity, glycaemic control, WHR, and gender were important determinants of dyslipidaemia in young diabetic patients. Diabet. Med. 18, 501-508 (2001)
Asunto(s)
Complicaciones de la Diabetes , Etnicidad , Hiperlipidemias/epidemiología , Adulto , Glucemia/análisis , China/etnología , Colesterol/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Estudios Transversales , Diabetes Mellitus/sangre , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Hemoglobina Glucada/análisis , Humanos , Hiperlipidemias/sangre , Hiperlipidemias/complicaciones , India/etnología , Malasia/epidemiología , Masculino , Prevalencia , Triglicéridos/sangreRESUMEN
Recent studies have shown that good glycaemic control can prevent the development of diabetic complications in type 1 and type 2 diabetes. We wished to observe the glycaemic control in patients from different centres in Peninsular Malaysia and the factors that determine it. We recruited 926 patients with diabetes diagnosed before age 40 years from seven different centres, with proportionate representation from the three main ethnic groups. Clinical history and physical examination were done and blood taken for HbA1c and fasting glucose. The overall glycaemic control was poor with geometric mean HbA1c of 8.6% whilst 61.1% of the patients had HbA1c greater than 8%. Glycaemic control in patients with type 2 diabetes varied between various centres and ethnic groups, with the best control obtained in Chinese patients. Significant predictors of HbA1c in both type 1 and type 2 diabetes include access to nurse educators, ethnic background and WHR. In type 2 diabetes, use of insulin was a significant predictor, while in type 1 diabetes, household income was a significant predictor. Socioeconomic status did not have a significant effect in type 2 diabetes. There were no significant differences in the glycaemic control in patients with different educational status. In conclusion, glycaemic control in big hospitals in Malaysia was poor, and was closely related to the availability of diabetes care facilities and ethnic group, rather than socioeconomic status.
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Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/terapia , Adulto , Demografía , Países en Desarrollo , Femenino , Accesibilidad a los Servicios de Salud , Humanos , Hiperglucemia/epidemiología , Hiperglucemia/terapia , Modelos Lineales , Malasia/epidemiología , Masculino , Clase SocialRESUMEN
This study determined the prevalence and significance of autoantibodies to GAD65 (GAD Ab), insulin (IAA), tyrosine-like phosphatase (IA2) and islet-cell (ICA) in a group of 213 young Malaysian Type 1 diabetics, diagnosed before the age of 40 years. Venous blood was taken at fasting, and at 6 minutes post-glucagon (1 mg i.v.). IAA was detected in 47.4%, GAD Ab in 33.8%, IA2 in 8.9% and ICA in 1.4% of the subjects. When based on post-glucagon C-peptide level of 600 pmol/L, 172 (80.7%) patients had inadequate pancreatic reserve, while the remainder 41(19.3%) showed normal response. The autoantibodies, either alone or in combination, were detectable in both groups of patients; higher prevalence in those with poor or no beta-cell function (73.3% versus 46.3%, p = 0.0001). Although the prevalence of GAD Ab was highest in newly diagnosed patients (< 5 years), unlike IA2 and ICA, the marker remained detectable in 24-25% of those patients with long-standing disease. Nineteen patients could probably belong to the "latent autoimmune diabetes in adults (LADA)" subset, where pancreatic reserve was adequate but patients had detectable autoantibodies and insulin-requiring. On the other hand, 68 of the 213 patients (32%) were seronegative, but presented with near or total beta-cell destruction. Thus, as has also been suggested by others, there is indeed etiological differences between the Asian and the Caucasian Type 1 diabetics, and, there is also the possibility that other, but unknown autoantigens are involved in causing the pancreatic damage.
Asunto(s)
Autoanticuerpos/análisis , Diabetes Mellitus Tipo 1/inmunología , Adolescente , Adulto , Niño , Preescolar , Femenino , Glutamato Descarboxilasa/inmunología , Humanos , Lactante , Insulina/inmunología , Islotes Pancreáticos/inmunología , Isoenzimas/inmunología , Malasia , Masculino , Persona de Mediana Edad , Proteína Tirosina Fosfatasa no Receptora Tipo 1 , Proteínas Tirosina Fosfatasas/inmunologíaRESUMEN
This study determined the prevalence of glutamic acid decarboxylase antibodies (GAD Ab) in a group of 926 young Malaysian diabetics of three ethnic groups, Malay, Chinese, and Indian. Patients were clinically diagnosed to be Type 1 or Type 2 before the age of 40 years. The overall GAD Ab positivity was 17.4% (161/926), significantly higher in the Type 1 than the Type 2 diabetics (35.5%, 116/329 vs. 7.5%, 45/597, P=0.0001). Compared to GAD Ab negative patients, seropositive diabetics were diagnosed at younger age (21.2+/-0.9 vs. 27.4+/-0.3 y, P=0.0001), had lower fasting (289+/-27.4 vs. 640+/-17.6 pmol/l, P=0.0001) and post-glucagon C-peptide levels (527+/-51.8 vs. 1030+/-28.9 pmol/l, P=0.0001). There were no racial differences in the prevalence of GAD Ab; of the total Type 1, 30.8, 36.4, and 39.4% were Malay, Chinese, and Indian diabetics, respectively and of the total Type 2, 8.8, 8.2, and 4.4% were Malay, Chinese, and Indian diabetics respectively. There was a curvilinear relationship between GAD Ab and the post-glucagon C-peptide levels, suggesting that GAD Ab do play a role in the beta-cells destruction and could be an important immune marker for the LADA group. This study reconfirmed previous reports that the autoimmune mechanisms in the Type 1 Asian diabetics are indeed different from the Caucasians, and further investigations should be carried out to explain the differences.
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Anticuerpos/análisis , Diabetes Mellitus/inmunología , Glutamato Descarboxilasa/inmunología , Adolescente , Adulto , Edad de Inicio , Anciano , Niño , Preescolar , China/etnología , Diabetes Mellitus/epidemiología , Diabetes Mellitus/etnología , Femenino , Humanos , India/etnología , Lactante , Malasia/epidemiología , Masculino , Persona de Mediana Edad , Estudios SeroepidemiológicosRESUMEN
This cross-sectional study looked at the prevalence of microalbuminuria and retinopathy in a cohort of 926 young, Type 1 and Type 2 diabetes mellitus (DM) patients, and determined the factors which were associated with these microvascular complications. The prevalence of microalbuminuria, defined as the albumin:creatinine ratio > or = 2.5 (for males) or > or = 3.5 mg/mmol (for females), was 13.4% in Type 1 DM, 69.5% in insulin-requiring Type 2 DM and 16% in Type 2 DM treated only with oral hypoglycemic agents. Compared to those with normal renal functions, these patients were older (P < or = 0.01), had significantly elevated blood pressures (P < 0.01 or P = 0.0001), and in the case of Type 1 DM, with a higher body mass index (P = 0.0001) and waist-hip ratio (P < 0.01). The prevalence of diabetic retinopathy in Type 1 DM was found to increase with the duration of diabetes, from 1.4% in the newly-onset (< 5 years), to 9.9% in those with 5-10 years disease, to 35% among patients with more than 10 years of diabetes (P < 0.0001). In this study, it was also observed that 10% of the Type 2 DM patients already had retinopathy within 5 years of diagnosis, and the prevalence increased significantly to 42.9% (P < 0.0001) among patients who had been diabetics for more than 10 years. Stepwise multiple regression analysis showed that besides the disease duration, systolic blood pressure was the most common and significant determinant for both microalbuminuria and retinopathy in both types of DM, thus implying that in order to reduce the risk of microvascular complications in diabetes mellitus, systolic and not just the diastolic blood pressure, should be effectively controlled.
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Albuminuria/etiología , Complicaciones de la Diabetes , Angiopatías Diabéticas/complicaciones , Retinopatía Diabética/etiología , Hipertensión/complicaciones , Adulto , Estudios Transversales , Diabetes Mellitus/orina , Diabetes Mellitus Tipo 1/complicaciones , Diabetes Mellitus Tipo 1/orina , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/orina , Humanos , Microcirculación , Persona de Mediana Edad , Sístole , Factores de TiempoRESUMEN
We have studied the effects of glucose on the release of somatostatin (SS), TRH and GHRH from incubated hypothalami of normal and genetically diabetic, Goto-Kakizaki (GK) rats. The active isomer D-glucose caused a dose-related inhibition of SS, TRH and GHRH from normal rat hypothalami over a 20-min incubation period in vitro. In contrast, in GK rats the effects of glucose on TRH and SS were significantly reduced and the effects on GHRH were abolished. These data indicate that the sensitivity of SS-, TRH- and GHRH-producing hypothalamic neurones is reduced in diabetic rats. The effect is most pronounced for GHRH release as there was no change in the release of this peptide with increasing glucose concentrations. In conclusion, it appears that the diabetic state in GK rats causes differential desensitisation (GHRH > TRH and SS) of neuronal responses to subsequent changes in glucose concentrations in vitro. This may be due to alterations in the neurotransmitter control and/or a reduction in number, affinity or function of glucose transporters on these peptidergic neurones or other intermediary neuronal pathways.
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Diabetes Mellitus/fisiopatología , Glucosa/farmacología , Hormona Liberadora de Hormona del Crecimiento/metabolismo , Hipotálamo/metabolismo , Hormonas Adenohipofisarias/metabolismo , Animales , Depresión Química , Relación Dosis-Respuesta a Droga , Hipotálamo/efectos de los fármacos , Masculino , Técnicas de Cultivo de Órganos , Ratas , Ratas Endogámicas , Ratas Wistar , Somatostatina/metabolismo , Hormona Liberadora de Tirotropina/metabolismoRESUMEN
In both fasting normal and diabetic subjects, nasally administered insulin achieves significant falls in plasma glucose concentrations. Repeated administration before and during a meal has been necessary to lower postprandial glycaemic excursion in subjects with NIDDM. We have studied the use of Novolin Nasal which employs a non-irritant, lecithin-based enhancer as a vehicle for human insulin, on postprandial glucose profiles in NIDDM subjects to determine efficacy, optimal dose frequency, and tolerability. Seventeen NIDDM subjects (15 men, 2 women) participated in a randomized, partially blinded, placebo-controlled, crossover trial of three active treatment regimens (nasal insulin, 120 U at 0 min, 60 U at 0 and +20 min or 120 U at +20 min) in relation to a standardized mixed meal given at 0 min. All active treatments significantly reduced postprandial glucose concentrations compared to placebo. Intranasal insulin given at 0 min at a dose of 60 U or 120 U resulted in a 50% reduction in postprandial incremental glucose compared to placebo over the first 2 h, whereas treatment with 60 U both at 0 and 20 min lead to a 70% reduction over the 240 min postprandial period. Post-prandial intravenous insulin was the least effective. There were no episodes of symptomatic hypoglycaemia. Local tolerability was excellent with only four reports of transient nasal irritation out of a total of 68 doses. The delivery device was accurate with intra-device CV of delivered dose of 4.8%.(ABSTRACT TRUNCATED AT 250 WORDS)
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Glucemia/metabolismo , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Insulina/administración & dosificación , Administración Intranasal , Glucemia/efectos de los fármacos , Estudios Cruzados , Ingestión de Alimentos , Ayuno , Femenino , Humanos , Insulina/farmacocinética , Insulina/uso terapéutico , Masculino , Persona de Mediana Edad , Placebos , Valores de Referencia , Método Simple Ciego , Factores de TiempoRESUMEN
OBJECTIVE: We wished to study alterations in serum insulin-like growth factor-I (IGF-I) and its binding proteins in subjects with insulin dependent diabetes mellitus (IDDM) and possible relations with metabolic and GH secretory status, before and after cholinergic modulation. In addition, we have investigated whether cholinergic modulation exerts any effects on IGF-I secretion, independently of any actions on GH secretory status. DESIGN: All subjects received GH releasing hormone (GHRH) 1-44; 80 micrograms i.v.) alone and 60 minutes following 120 mg of pyridostigmine orally or 200 mg of pierenzepine orally. The three tests were carried out in random order at least one week apart. Blood was sampled at 15-minute intervals over 120 minutes. PATIENTS: Twelve male subjects with IDDM and no clinical evidence of complications were selected on the basis of HbA1 levels to provide a wide range of metabolic control. Six normal male subjects were also studied. MEASUREMENTS: Serum IGF-I, IGF-binding protein 1 (IGFBP-1) and IGFBP-3 were measured at regular intervals throughout the study. Fasting plasma glucose and HbA1 were measured before each study to provide measures of metabolic control. RESULTS: Serum IGF-I and IGFBP-3 levels were significantly lower while serum IGFBP-I levels were significantly higher in the diabetic subjects. Pirenzepine had no effect on serum IGF-I, IGFBP-1 or IGFBP-3 in diabetic subjects but caused a significant increase in serum IGF-I and IGFBP-3 levels in normal subjects. Pyridostigmine had no effect on IGF-I, IGFBP-1 or IGFBP-3 in either diabetic or normal subjects. IGFBP-1 levels were significantly correlated with fasting plasma glucose but no correlation was demonstrated between measures of diabetic control and serum IGF-I or IGFBP-3 levels in diabetic subjects, nor was there any correlation between GH responses to GHRH alone or after pirenzepine or pyridostigmine pretreatment and serum levels of IGF-I, IGFBP-1 or IGFBP-3. CONCLUSION: These data confirm that subjects with IDDM have reduced serum IGF-I and IGFBP-3 and increased IGFBP-1 levels, the latter being directly related to the fasting plasma glucose concentrations. The absence of any relation between changes in the IGF-I system and altered GH neuroregulation after cholinergic modulation suggests that changes in IGF-I are not the sole contributors to the altered GH neuroregulation which occurs in IDDM. We have also shown an acute stimulatory effect of pirenzepine on serum IGF-I and IGFBP-3 in normal subjects which is not present in IDDM although the underlying mechanisms is unknown.
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Proteínas Portadoras/sangre , Diabetes Mellitus Tipo 1/sangre , Factor I del Crecimiento Similar a la Insulina/metabolismo , Glucemia/metabolismo , Hormona Liberadora de Hormona del Crecimiento/farmacología , Humanos , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina , Masculino , Pirenzepina/farmacología , Bromuro de Piridostigmina/farmacología , Estimulación Química , Factores de TiempoRESUMEN
OBJECTIVES: Pirenzepine, a selective muscarinic cholinergic antagonist, reduces plasma insulin and plasma glucose responses to a mixed meal in a dose dependent fashion in normals and in patients with non-insulin dependent diabetes. We have studied the effects of pirenzepine on plasma insulin, plasma glucose, growth hormone (GH), androstenedione, testosterone, insulin-like growth factor-I (IGF-I) and IGF binding protein 1 (IGFBP-1) responses to a mixed meal in obese clinically hyperandrogenic women with the polycystic ovary syndrome. SUBJECTS AND METHODS: Six obese women with polycystic ovary syndrome (BMI range 27.3-39.8 kg/m2) were studied in random sequence, and received either placebo or pirenzepine (single doses of 50, 100, or 200 mg) one hour before a standard test meal. Blood was sampled every 15 minutes for 2 hours after the meal and every 30 minutes thereafter for a total of 4 hours. RESULTS: Mean fasting plasma insulin concentrations were increased. Peak post-prandial plasma insulin concentrations were reduced significantly by all three doses used. Post-prandial integrated plasma insulin concentrations were reduced by the two higher doses. Peak post-prandial plasma glucose concentrations were also reduced. The late post-prandial GH surge was significantly suppressed by all three doses. However, plasma androstenedione, testosterone, IGF-I and IGFBP-1 concentrations were not significantly different when placebo was compared with pirenzepine 200 mg. CONCLUSIONS: Acute cholinergic muscarinic blockade with pirenzepine significantly reduces meal stimulated plasma insulin and plasma glucose concentrations in clinically hyperandrogenic women with polycystic ovary syndrome. The ability of pirenzepine to reduce plasma insulin without worsening glycaemia is a particular advantage and may be therapeutically relevant. Further studies are under way to assess the usefulness of pirenzepine in long-term suppression of plasma insulin in this group of patients.
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Glucemia/metabolismo , Ingestión de Alimentos/fisiología , Insulina/sangre , Obesidad/sangre , Pirenzepina/farmacología , Síndrome del Ovario Poliquístico/sangre , Adulto , Androstenodiona/sangre , Proteínas Portadoras/análisis , Relación Dosis-Respuesta a Droga , Femenino , Hormona del Crecimiento/sangre , Humanos , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina , Factor I del Crecimiento Similar a la Insulina/análisis , Testosterona/sangreRESUMEN
Recent work in healthy subjects, the aged, and subjects with gestational diabetes or drug-induced insulin resistance using minimal model analysis of the tolbutamide-modified frequently sampled intravenous glucose tolerance test suggested that a reduced sampling regimen of 12 time points produced unbiased and generally acceptable estimates of insulin sensitivity (SI) and glucose effectiveness (SG) compared with a full sampling schedule of 30 time points. We have used data from 26 insulin-modified frequently sampled intravenous glucose tolerance tests in 21 subjects with NIDDM to derive and compare estimates of SI and SG from the full sampling schedule (SI(30), SG(30)) with those estimated from the suggested 12 time points (SI(12), SG(12)) and those estimated with the addition of a 25-min time point (SI(13), SG(13)). Percentage relative errors were calculated relative to the corresponding 30 time-point values. A statistically significant bias of 15% (97% confidence interval from 7.4 to 25.6%, interquartile range 25%) was introduced by the estimation of SI(12) but not SI(13) (1%, 97% confidence interval from -9.4 to 9.3%, interquartile range 21%). Results for SG(12) (-12%, 97% confidence interval from -46.7 to 1.2%, interquartile range 49%) and SG(13) (-5%, 97% confidence interval from -27.8 to 6.8%, interquartile range 37%) were statistically equivocal. The precision of estimation of SI(12), SG(12), and SG(13) measured by the interquartile range of the percentage relative errors was poor. The precision of determination measured by the median minimal model coefficient of variation was 18, 29, and 27% for SI(30), SI(12), and SI(13) and 9, 11, and 11% for SG(30), SG(12), and SG(13), respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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Glucemia/análisis , Diabetes Mellitus Tipo 2/sangre , Resistencia a la Insulina/fisiología , Insulina/farmacología , Adulto , Anciano , Protocolos Clínicos , Diabetes Mellitus Tipo 2/fisiopatología , Femenino , Prueba de Tolerancia a la Glucosa/métodos , Prueba de Tolerancia a la Glucosa/normas , Humanos , Masculino , Persona de Mediana Edad , Modelos Biológicos , Muestreo , Sesgo de SelecciónRESUMEN
OBJECTIVE: We have investigated the effects of cholinergic modulation with pirenzepine and pyridostigmine and of GH pretreatment on the subsequent GH response to a maximal stimulatory dose of GH-releasing hormone (GHRH) in patients with insulin dependent diabetes mellitus (IDDM). We have also investigated the relationship between the differences in metabolic control and other parameters of disease state with the differences in GH responses in IDDM. PATIENTS: Thirteen male subjects with IDDM and no clinical evidence of complications were selected based on HbA1 levels to provide a wide range of metabolic control. Seven normal subjects were also studied. DESIGN: Twelve of the subjects with IDDM and six normal subjects received pirenzepine 200 mg and pyridostigmine 120 mg pretreatment 60 minutes and GH pretreatment 3 hours before an i.v. injection of GHRH (1-44) (80 micrograms) in random order. All subjects underwent a control study with GHRH alone. MEASUREMENTS: Serum GH and plasma glucose were measured at regular intervals throughout the study. Fasting plasma glucose and HbA1 were measured before each study to provide measures of metabolic control. RESULTS: Subjects with IDDM demonstrated exaggerated GH responses to GHRH compared to normals. Pirenzepine significantly reduced GH responses in both normal and diabetic subjects. However, the GH response to GHRH after pirenzepine was higher in subjects with IDDM (mean GH:IDDM vs normals; 8.1 +/- 1.3 vs 2.9 +/- 0.7 mU/l, P < 0.05). Pyridostigmine 120 mg significantly augmented the GH response to GHRH in normal subjects. In diabetic subjects, pyridostigmine failed to increase GH response to GHRH compared to GHRH alone (mean GH: pyridostigmine vs control: 75.7 +/- 12.6 vs 38.9 +/- 5.4 mU/l, P = NS). GH responses to GHRH after pyridostigmine pretreatment in both normal and diabetic subjects did not differ and the GH response to GHRH after pyridostigmine in normal subjects did not differ from the GH response to GHRH alone in diabetic subjects. In normal subjects, GH pretreatment significantly reduced subsequent GH responsiveness to GHRH (delta peak GH 26.4 +/- 5.2 vs 7.7 +/- 5.4 mU/l, P < 0.04). In contrast, GH pretreatment did not cause any significant reduction in GH responsiveness to GHRH in diabetics (delta peak GH 53.6 +/- 9.7 vs 33.4 +/- 11 mU/l, P = NS). No significant correlation was demonstrated between measures of diabetic control and the responses to GHRH alone or after cholinergic modulation and GH pretreatment. CONCLUSION: These data suggest that ambient hypothalamic cholinergic tone in diabetes is high, and of similar degree to the enhanced cholinergic tone in normal subjects pretreated with pyridostigmine. We suggest that in diabetic subjects, the reduced responsiveness to autofeedback may be secondary to the enhanced cholinergic tone demonstrated in these patients. The mechanisms linking the uncontrolled diabetic state to this abnormal neuroregulation of GH remains unknown at present.
Asunto(s)
Inhibidores de la Colinesterasa/farmacología , Diabetes Mellitus Tipo 1/fisiopatología , Hormona Liberadora de Hormona del Crecimiento/farmacología , Hormona del Crecimiento/metabolismo , Hipotálamo/metabolismo , Adulto , Glucemia/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Retroalimentación , Hormona del Crecimiento/farmacología , Humanos , Masculino , Persona de Mediana Edad , Pirenzepina/farmacología , Bromuro de Piridostigmina/farmacología , Somatostatina/metabolismoRESUMEN
OBJECTIVE: We wished to examine the effects of ambient glycaemia on hypothalamic somatostatinergic tone in insulin-dependent diabetes mellitus. DESIGN: After 6-hour periods of either euglycaemia (5 mmol/l) or hyperglycaemia (15 mmol/l), exercise-induced GH secretion was measured. PATIENTS: Seven insulin dependent diabetics with no evidence of complications were recruited. RESULTS: There was no significant difference between basal GH levels during euglycaemia and hyperglycaemia (5.50 vs 5.53 mU/l). Nor was there a significant difference when mean delta GH levels (33.9 vs 27.4 mU/l) or mean area under GH curve (2331 vs 4038 mU min/l) during euglycaemia or hyperglycaemia were compared. CONCLUSIONS: We find no evidence therefore to support short-term effects of ambient glucose concentration on GH responsiveness, and by inference no direct effect of short-term changes in glycaemic control on hypothalamic release of somatostatin in the aetiology of GH hypersecretion in insulin-dependent diabetes mellitus.