RESUMEN
Physiological changes of pregnancy include insulin resistance and activation of the innate immunity with an inflammatory response. The working hypothesis is that the sub-clinical inflammation associated with excessive adiposity may favor the development of gestational diabetes (GDM) and Type 2 diabetes and other metabolic abnormalities related to cardiovascular disease later in life. In this paper we review the complex interrelationship among inflammatory markers, metabolic syndrome, and endothelium dysfunction in women with GDM and discuss if women with previous GDM (pGDM) could be considered at risk for cardiovascular diseases. MEDLINE was searched for articles relating GDM and the adipokines (tumor necrosis factor-alpha and adiponectin) as well as the acute-phase inflammatory biomarker C-reactive protein that contribute to the development of diabetic pregnancy and vascular complications. However, to date, in pGDM women no prospective study is available, to corroborate the hypothesis that inflammatory pattern could be taken as predictor of cardiovascular disease later in life. Therefore, our paper should provide arguments to perform follow-up programs to prevent cardiovascular events in women with pGDM. Control of body weight, regular physical exercise are indeed powerful intervention tools able at improving insulin sensitivity and reduce sub-clinical inflammation, both involved in the pathogenesis of cardiovascular disease.
Asunto(s)
Diabetes Gestacional/inmunología , Diabetes Gestacional/metabolismo , Angiopatías Diabéticas/inmunología , Angiopatías Diabéticas/metabolismo , Inflamación/inmunología , Inflamación/metabolismo , Factores de Edad , Envejecimiento/inmunología , Envejecimiento/metabolismo , Enfermedades Cardiovasculares/inmunología , Enfermedades Cardiovasculares/metabolismo , Femenino , Humanos , EmbarazoRESUMEN
AIM: The aim of this paper was to describe signs and performance of multislice computed tomography (MSCT) in patients with acute mesenteric infarction (AMI). METHODS: MSCT examinations of 26 patients with AMI and of 34 patients with acute abdomen and surgical diagnosis excluding AMI were retrospectively analyzed. All studies were performed with arterial and portal venous phase scans, 2.5 mm thickness, 1.25 mm image interval. All abnormal findings at MSCT in patients with AMI were recor- ded. Patients with MSCT evidence of mesenteric artery occlusion or pneumatosis or venous gas or, alternatively, bowel thicken-ing associated with lack of wall enhancement or venous thrombosis or parenchimal infarction were considered to be affected by AMI. RESULTS: AMI was due to mesenteric artery thrombosis in 17 patients, mesenteric vein thrombosis in 7, and nonocclusive ischemia in 2. In 16/17 patients arterial thrombosis was visualized, in 7/7 venous thrombosis was found. Portal or mesenteric vein gas was seen in 5% and pneumatosis in 38%; bowel wall thickening associated with other signs was found in 31%. Sensitivity and specificity were 92% and 100%, respectively. CONCLUSIONS: MSCT allows an accurate assessment of the mesenteric circulation and the bowel wall. This makes possible optimal visualization of signs of AMI resulting in a good clinical performance.
Asunto(s)
Isquemia/diagnóstico por imagen , Isquemia/cirugía , Arterias Mesentéricas , Venas Mesentéricas , Mesenterio/irrigación sanguínea , Tomografía Computarizada por Rayos X , Enfermedad Aguda , Humanos , Isquemia/etiología , Estudios Retrospectivos , Tomografía Computarizada por Rayos X/métodosRESUMEN
We investigated intracellular processing of the insulin-receptor complex in monocytes from 12 healthy control subjects, 11 obese nondiabetic subjects, and 13 obese patients with non-insulin-dependent diabetes mellitus (NIDDM) by measuring receptor internalization, recovery of cell-surface insulin binding after receptor internalization, and the release of intracellular intact insulin (insulin retroendocytosis). When monocytes from the three groups of subjects were exposed to 100 nM unlabeled insulin for 30 min at 37 degrees C, the subsequent cell-surface 125I-labeled insulin binding was reduced, but the total number of insulin receptors, measured by radioimmunoassay, was not changed. These findings indicate a redistribution of insulin receptors from the surface to the cell interior. Insulin-receptor internalization was significantly lower in monocytes of obese NIDDM patients (mean +/- SE 17.8 +/- 4.7%) than in obese subjects and healthy control subjects (33.5 +/- 4.5%, P less than .05, and 34.4 +/- 3.7%, P less than .02, respectively). Moreover, in downregulated cells, a complete recovery of the initial insulin binding was observed in control subjects but not in obese NIDDM patients or obese nondiabetic subjects. The release of internalized insulin was also reduced in obese NIDDM patients and obese subjects (t 1/2 = 49.0 +/- 2.4 min, P less than .02; 47.4 +/- 5.7 min, P less than .05; and 32.9 +/- 3.8 in NIDDM patients, obese subjects, and control subjects, respectively). In the radioactivity released from monocytes of obese subjects and obese NIDDM patients, the percentage of intact insulin was higher (P less than .05) than in control subjects, suggesting reduced intracellular insulin degradation in obese subjects and obese NIDDM patients.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus/sangre , Monocitos/metabolismo , Obesidad/sangre , Procesamiento Proteico-Postraduccional , Receptor de Insulina/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Femenino , Humanos , Insulina/uso terapéutico , Cinética , Masculino , Persona de Mediana Edad , Receptor de Insulina/genética , Valores de ReferenciaRESUMEN
The products of insulin metabolism generated in vitro and in vivo were compared in this study. Monocytes from 10 control subjects were incubated with 125IA14-labeled insulin, acid washed, and solubilized or reincubated in insulin-free binding buffer to study both intracellular radioactivity or radioactivity released from cells to medium. To evaluate in vivo insulin metabolism, labeled insulin (100-120 microCi) was injected as a single intravenous bolus in 5 of the 10 subjects. Cellular and plasma radioactivity was characterized by high-performance liquid chromatography (HPLC). The results of the study show the following: 1) Products with superimposable HPLC elution profiles are found within cells and in medium. Two new labeled products are observed in the latter, suggesting that a membrane degradation process exists in monocytes. 2) Intermediates found within monocytes, in medium from monocytes, and in plasma have identical elution profiles, supporting the possibility that insulin is metabolized in various cells by a common pathway. 3) Insulin metabolism produces intermediates that bind well to anti-insulin antibody. The presence in plasma of these products induces a significant difference in the value of the metabolic clearance rate of insulin when HPLC or immunoprecipitation is used to detect intact insulin. 4) Immunoprecipitable products maintain, in part, the capacity to bind to insulin receptors and to be internalized into monocytes.
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Insulina/sangre , Leucocitos Mononucleares/metabolismo , Cromatografía Líquida de Alta Presión , Humanos , Técnicas In Vitro , Inyecciones Intravenosas , Insulina/administración & dosificación , Insulina/análogos & derivados , Radioisótopos de Yodo , Cinética , Masculino , Técnica de Dilución de Radioisótopos , Valores de Referencia , Factores de TiempoRESUMEN
This study investigated the relative effect of obesity alone and in combination with non-insulin-dependent diabetes mellitus (NIDDM) on the intracellular processing of insulin and evaluated the effect of metformin therapy on this process. Monocytes from 11 obese hyperinsulinemic subjects, 13 obese hyperinsulinemic NIDDM patients, and 7 nondiabetic control subjects were incubated with A14-125I-labeled insulin for 60 min at 37 degrees C, and intracellular insulin degradation was characterized by high-performance liquid chromatography. Total cell-associated insulin (insulin binding) and internalized and degraded insulin were decreased in obese subjects and significantly decreased in obese NIDDM patients compared with nondiabetic control subjects. In NIDDM patients, intracellular insulin degradation was inversely correlated with fasting plasma glucose (P less than 0.01). Eight obese subjects and 9 obese NIDDM patients were restudied after 4 wk of therapy with metformin (850 mg twice a day). Plasma levels of the drug were superimposable in the two groups. Metformin therapy did not change glucose and insulin levels in obese subjects but caused a decrease in blood glucose in obese NIDDM patients. Total cell-associated radioactivity (insulin binding) significantly increased in both groups (P less than 0.01). On the contrary, internalized radioactivity increased (0.83 +/- 0.3 vs. 1.31 +/- 0.35%, P less than 0.01), and similarly, insulin degradation was enhanced (54.6 +/- 8.9 vs. 74.22 +/- 9.15%, P less than 0.01) only in monocytes from obese NIDDM patients. However, the levels of these parameters were still lower than in control subjects (internalization, 2.94 +/- 0.68%; degradation, 93.03 +/- 3.7%).(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus/sangre , Insulina/sangre , Metformina/farmacología , Monocitos/metabolismo , Transporte Biológico/efectos de los fármacos , Glucemia/metabolismo , Humanos , Cinética , Persona de Mediana Edad , Monocitos/efectos de los fármacos , Obesidad/sangre , Valores de ReferenciaRESUMEN
We studied total cell-associated A14-[125I]insulin radioactivity (including surface-bound and internalized radioactivity), insulin internalization, and its intracellular degradation at 37 C in monocytes from nonobese type II untreated diabetic patients (n = 9) and normal subjects (n = 7). Total cell-associated radioactivity was decreased in diabetic patients [2.65 +/- 1.21% (+/- SD) vs. 4.47 +/- 1.04% of total radioactivity; P less than 0.01]. Insulin internalization was also reduced in diabetic patients (34.0 +/- 6.8% vs. 59.0 +/- 11.3% of cell-associated radioactivity; P less than 0.01). Using high performance liquid chromatography six intracellular forms of radioactivity derived from A14-[125I] insulin were identified; 10-20% of intracellular radioactivity had approximately 300,000 mol wt and was identified as radioactivity bound to the insulin receptor, and the remaining intracellular radioactivity included intact A14-[125I]insulin, [125I]iodide, or [125I]tyrosine, and three intermediate compounds. A progressive reduction of intact insulin and a corresponding increase in iodine were found when the incubation time was prolonged. Intracellular insulin degradation was reduced in monocytes from diabetic patients; intracellular intact insulin was 65.6 +/- 18.1% vs. 37.4 +/- 18.0% of intracellular radioactivity (P less than 0.01) after 2 min and 23.6 +/- 22.3% vs. 3.9 +/- 2.3% (P less than 0.01) after 60 min in diabetic patients vs. normal subjects, respectively. In conclusion, 1) human monocytes internalize and degrade insulin in the intracellular compartment in a stepwise time-dependent manner; and 2) in monocytes from type II diabetic patients total cell-associated radioactivity, insulin internalization, and insulin degradation are significantly reduced. These defects may be related to the cellular insulin resistance present in these patients.
Asunto(s)
Diabetes Mellitus Tipo 2/sangre , Insulina/sangre , Monocitos/metabolismo , Anciano , Cromatografía en Gel , Cromatografía Líquida de Alta Presión , Femenino , Humanos , Técnicas de Inmunoadsorción , Yoduros/sangre , Radioisótopos de Yodo , Cinética , Masculino , Persona de Mediana Edad , Tirosina/sangreRESUMEN
Haptoglobin (Hp) is a glycoprotein involved in the acute phase response to inflammation. Our previous findings indicate that Hp mRNA and protein are present in the adipose tissue of rodents and that Hp gene expression is up-regulated in obese models. The aim of the present study was to establish whether Hp could be considered a marker of obesity in humans. In 312 subjects, serum Hp was correlated directly with body mass index (BMI), leptin, C-reactive protein (CRP), and age. In a multivariate stepwise regression analysis, BMI and CRP were independent determinants of serum Hp in females, with BMI having the strongest effect. CRP and age were independent determinants of serum Hp in males, although explaining only a modest percentage of the total variability. Serum Hp was positively associated with body fat, as assessed by dual-energy x-ray absorptiometry, both in female and in male groups. The level of significance improved when serum Hp was analyzed against fat mass adjusted for lean mass. Finally, Northern and Western blot analyses performed in biopsies of sc abdominal fat from 20 obese individuals showed the presence of Hp mRNA and protein in the human adipose tissue. In conclusion, serum Hp constitutes a novel marker of adiposity in humans, and the adipose tissue likely contributes to determine its levels.
Asunto(s)
Tejido Adiposo/metabolismo , Índice de Masa Corporal , Haptoglobinas/metabolismo , Obesidad/sangre , Adolescente , Adulto , Anciano , Biomarcadores/sangre , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Obesidad/diagnósticoRESUMEN
Metabolic abnormalities occur in biguanide-treated diabetic patients. We investigated the relationship between plasma metformin and phenformin concentrations and metabolic effects. Drug levels were measured in 37 type II diabetic patients by HPLC. The method was sensitive, specific, and linear over a wide range of drug concentrations. Metformin and phenformin values ranged from 236 to 718 ng/ml and from 28 to 114 ng/ml, respectively. The plasma metformin level was correlated with triglycerides (r = -0.55; P less than 0.05) but not with drug dosage, plasma glucose, HbA1, creatinine, creatinine clearance, lactate, pyruvate, lipid, and clinical parameters. Plasma phenformin concentrations correlated with lactate (r = 0.49; P less than 0.05) and HbA1 (r = 0.50; P less than 0.05) but not with drug dosage, parameters of diabetes control, creatinine, creatinine clearance, pyruvate, and clinical parameters. The clinical usefulness of this HPLC method, the evidence that the increase of lactate is related to the circulating phenformin levels, and the demonstration that the metformin effect on triglyceride metabolism is correlated to plasma drug levels are the positive findings of this work.
Asunto(s)
Diabetes Mellitus Tipo 2/sangre , Metformina/sangre , Fenformina/sangre , Anciano , Glucemia , Cromatografía Líquida de Alta Presión , Creatinina/análisis , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Femenino , Humanos , Lactatos/sangre , Masculino , Metformina/uso terapéutico , Persona de Mediana Edad , Fenformina/uso terapéutico , Piruvatos/sangre , Triglicéridos/sangreRESUMEN
OBJECTIVE: Chinese hamster ovary (CHO) cells transfected with human engineered insulin receptor (IR) cDNA to mutate Cys 860 to Ser (CHO-IR(C860S)) showed a defective insulin internalization without affecting insulin binding and IR autophosphorylation. Moreover, this mutation reduces insulin receptor substrate (IRS)-1 tyrosine phosphorylation and insulin-induced metabolic and mitogenic effects. Altogether, these observations support a role of the extracellular domain of IR beta-subunit in insulin and receptor intracellular targeting as well as in insulin signaling. DESIGN AND METHODS: This study assesses in more details the effect of IR(C860S) mutation on the trafficking of the insulin-IR complex. In particular, IR internalization, phosphorylation, dissociation and recycling, as well as insulin degradation and retroendocytosis have been investigated in CHO cells overexpressing either wild type (CHO-IR(WT)) or mutated IRs. RESULTS: the C860S mutation significantly decreases IR internalization both insulin stimulated and constitutive. In spite of a similar dissociation of internalized insulin-IR complex, recycling of internalized IR was significantly faster (half life (t(1/2)): 21 min vs 40 min, P<0.001) and more extensive (P<0.01) for IR(C860S) than for IR(WT). On the other hand, insulin degradation and retroendocytosis were superimposable in both cell lines. As expected, insulin-induced phosphorylation was similar in both IRs, however dephosphorylation was much more rapid and was greater (P<0.01) in CHO-IR(WT) as compared with CHO-IR(C860S) cells. CONCLUSIONS: Transmembrane and intracellular domain of IR seem to be determinants for IR internalization. Now we report that Cys 860 in the IR beta-subunit ectodomain may be of relevance in ensuring a proper internalization and intracellular trafficking of the insulin-IR complex.
Asunto(s)
Espacio Extracelular/metabolismo , Insulina/metabolismo , Receptor de Insulina/fisiología , Animales , Células CHO , Cricetinae , Semivida , Humanos , Fosforilación , Fosfotirosina/metabolismo , Receptor de Insulina/genética , Receptor de Insulina/metabolismo , TransfecciónRESUMEN
Dissociation of the insulin-insulin receptor complex plays a crucial role in the processing of both insulin and the insulin receptor, and the acidification of endocytic vesicles may be the mechanism by which internalized insulin is dissociated from its receptor and properly sorted and processed. Internalized insulin-insulin receptor complexes are abnormally processed in cells from patients with non-insulin-dependent diabetes mellitus (NIDDM). Accordingly, to further investigate the mechanisms of the derangements observed in NIDDM cells, we examined the effects of the ionophore monensin, which inhibits endosomal acidification, on the cellular processing of insulin and insulin receptor in monocytes from control subjects (n = 12) and NIDDM patients (n = 14). This study confirms that monocytes from NIDDM patients, compared with cells from normal controls, had reduced binding (P < .01), internalization (P < .01), and degradation (P < .01) of insulin. In addition, the release of intracellular radioactivity was slower (P < .01), and recycling of the insulin receptor was inhibited (P < .01). Moreover, these defects were associated with a significant (P < .01) decrease of dissociation of the internalized insulin-insulin receptor complex. In cells from normal controls, incubation with monensin decreased insulin binding (P < .01), but not insulin internalization. High-performance liquid chromatography (HPLC) analysis of intracellular radioactivity showed that after monensin intracellular intact insulin significantly increased (P < .01), thus suggesting a decrease of intracellular insulin degradation. Moreover, insulin receptor recycling was completely disrupted. All of these derangements were associated with a significant decrease (P < .01) of dissociation of insulin-insulin receptor complexes. On the contrary, in diabetic monocytes, monensin had no significant additional effect on NIDDM-linked alterations. Comparison of the results obtained in cells from NIDDM patients to those found in monensin-treated normal cells demonstrates that NIDDM and monensin gave rise to a superimposable impairment of dissociation of the intracellular insulin-insulin receptor complex, associated with similar abnormal sorting and processing of insulin and its receptor. The only defect present in NIDDM cells but not in monensin-treated cells is the decrease of insulin internalization, which thus seems independent of the action of monensin on the processing of internalized insulin-insulin receptor complex. These results suggest that the impairment of dissociation of the insulin-insulin receptor complex may play a crucial role in the subsequent altered processing of insulin and insulin receptor. Moreover, they raise the question as to a possible similar alteration of the same intracellular mechanism by NIDDM and monensin, and point out that the derangements found in cells from NIDDM patients could be localized within the endosomal apparatus and consist mainly of a defective acidification of its interior.
Asunto(s)
Diabetes Mellitus Tipo 2/sangre , Endocitosis/fisiología , Endosomas/metabolismo , Insulina/análogos & derivados , Monocitos/metabolismo , Receptor de Insulina/metabolismo , Cromatografía Líquida de Alta Presión , Estudios de Cohortes , Diabetes Mellitus Tipo 2/fisiopatología , Endocitosis/efectos de los fármacos , Endosomas/efectos de los fármacos , Humanos , Insulina/metabolismo , Radioisótopos de Yodo , Ionóforos/análisis , Ionóforos/metabolismo , Ionóforos/farmacología , Persona de Mediana Edad , Monensina/análisis , Monensina/metabolismo , Monensina/farmacología , Monocitos/efectos de los fármacos , Unión Proteica/efectos de los fármacos , Unión Proteica/fisiología , Receptor de Insulina/efectos de los fármacos , Valores de Referencia , Factores de TiempoRESUMEN
Tolerance to an oral tryptophan load (50 mg/kg body weight) was evaluated in a group of 15 insulin-dependent diabetic patients of both sexes in poor metabolic control. Tryptophan was measured fluorometrically, and the plasma levels of the other physiological amino acids were determined by HPLC. The ratio of the plasma concentration of each large neutral amino acid (LNAA) to the sum of the others was calculated to serve as an index for the competitive transport of these amino acids into the brain. The results show that post-loading plasma tryptophan levels in diabetic patients increased less than in healthy controls, suggesting enhanced liver catabolism of this amino acid (as reported for diabetic animals). Small changes were observed in the post-loading plasma concentrations of other amino acids. Therefore, the increment in the tryptophan/LNAA ratio in controls (basal, 0.12 +/- 0.01; 120 min after the load, 0.89 +/- 0.04; 240 min, 0.51 +/- 0.03) was greatly attenuated in diabetic patients (basal, 0.11 +/- 0.01, NS; 120 min, 0.46 +/- 0.04, p < 0.01; 240 min, 0.31 +/- 0.04, p < 0.01). Post-loading excursions in some other ratios were slightly larger in control than diabetic subjects. These differences, which may occur to a lesser extent after a protein-rich meal, could modify the availability of precursor amino acids to the brain for synthesis of neurotransmitters. Thus, as happens in certain animal species, an impairment of the post-absorptive accumulation of tryptophan and serotonin in the brain may occur in diabetic patients as a result of altered metabolic disposal of tryptophan.
Asunto(s)
Aminoácidos/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Quinurenina/metabolismo , Triptófano , Adulto , Análisis de Varianza , Estudios de Casos y Controles , Femenino , Humanos , Quinurenina/orina , Masculino , Triptófano/orinaRESUMEN
In order to evaluate the prevalence of gestational diabetes mellitus (GDM) and the presence of risk factors for GDM, we conducted a retrospective study of a cohort of Italian women. In addition, we compared universal versus selective screening to validate the ADA's recommendations in our population. From June 1st, 1995 to December 31st, 2001, universal screening for GDM was performed in 3950 women. The glucose challenge test (GCT) was positive (GCT+) in 1389 cases (35.2%). The 1-h glucose level after GCT enabled us to diagnose GDM directly in 24 pregnant women. Oral glucose tolerance test (OGTT) was performed in 1221 GCT+ women (144 cases with GCT+ dropped out) and GDM was diagnosed in 284 (23.2%) of them. OGTT was also performed in 391 randomly chosen, women from the GCT negative (GCT-) group. In this last group 25 (6.3%) women had GDM. Thus, the total number of subjects with GDM was 333 out of 3806 with a prevalence of 8.74% in the entire cohort. Assuming that the rate of GDM observed in the random sample of GCT- women is applicable to the whole group of 2561 GCT- women, then 161 GCT- patients could also have GDM. This will further increase the estimated prevalence for the whole cohort up to 12.3% (i.e. 469 out of 3806 pregnant women). There were 236 (5.6%) women with a low risk for GDM (normal weight, age less than 25 years and without a family history of diabetes). In this group we found 34 cases and five cases with positive screening test and GDM, respectively. Thus, if we excluded low risk women from the screening test, as suggested by ADA recommendations, only five women with GDM would have been missed. However, about 95% of our population were at medium or high risk for GDM and, therefore, would have been screened. The rate of GDM was significantly higher in women with a positive history of diabetes, increasing age, previous pregnancies, pre-pregnancy overweight and short stature. After logistic regression analysis, GDM diagnosis was significantly correlated with age (P<0.0001), pre-pregnancy BMI (P<0.0001), weight gain (P<0.0001) and family history of diabetes (P<0.01).
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Diabetes Gestacional/epidemiología , Adulto , Estatura , Peso Corporal , Diabetes Gestacional/sangre , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Italia/epidemiología , Tamizaje Masivo/métodos , Paridad , Embarazo , Prevalencia , Factores de Riesgo , Sociedades MédicasRESUMEN
In this study we investigated whether the presence of diabetic autonomic neuropathy (DAN) leads to an altered composition of saliva. DAN was evaluated in 33 normal subjects and 31 diabetic patients by means of the Valsalva manoeuvre, R-R variation during deep breathing, heart rate response to standing and lying down and blood pressure response to standing. Salivary flow (ml/h), salivary glucose levels (mumol/l) and salivary glucose secretory rate (mumol/h) were measured in each subject. Twelve diabetic patients were positive for DAN. Salivary flow (13 +/- 2 ml/h) and glucose concentration (330 +/- 50 mumol/l) were not significantly lower in patients with DAN than in normal subjects (18 +/- 2 ml/h, 500 +/- 50 mumol/l) and diabetic patients without DAN (16 +/- 1.9 ml/h, 500 +/- 40 mumol/l). The salivary glucose secretion rate was significantly lower (P less than 0.02) in diabetic patients with DAN (4.2 +/- 1.0 mumol/h) than in normal subjects and diabetic patients without DAN (9.0 +/- 1.0 mumol/h and 8.0 +/- 0.9 mumol/h respectively). The test had a good sensitivity and specificity, and appeared to be particularly indicated in discriminating patients without DAN. It is suggested that the measurement of salivary glucose may represent a simple, quick and inexpensive method for the screening of diabetic autonomic neuropathy.
Asunto(s)
Enfermedades del Sistema Nervioso Autónomo/diagnóstico , Neuropatías Diabéticas/diagnóstico , Glucosa/metabolismo , Glándulas Salivales/metabolismo , Adulto , Enfermedades del Sistema Nervioso Autónomo/etiología , Presión Sanguínea , Femenino , Glucosa/análisis , Frecuencia Cardíaca , Humanos , Masculino , Respiración , Saliva/análisis , SalivaciónRESUMEN
There is evidence that intracellular insulin may carry out some insulin mediated actions, including glucose transport. As intracellular insulin has never been quantitatively assessed in human cells, we evaluated its concentrations in monocytes from normal subjects (n = 7) and obese patients without (n = 9) and with Type 2 diabetes mellitus (n = 10). After the incubation of cells with labeled insulin for 60 min at 37 degrees C, intracellular intact insulin concentrations were measured by HPLC and expressed as pmol x 10(-6). Insulin concentrations were higher (ANOVA P < 0.01) within cells from obese (115.4 +/- 26.4 pmol x 10(-6)/2 x 10(5) cells) and obese diabetic patients (93.2 +/- 36.3 pmol x 10(-6)/2 x 10(5) cells) compared with normal cells (28.5 +/- 13.1 pmol x 10(-6)/2 x 10(5) cells). Moreover, after insulin was removed from the incubation medium the decrease of intracellular insulin was significantly lower (P < 0.01) in cells from both obese and obese diabetic patients than in normal subjects. Intracellular undissociated insulin-insulin receptor complexes on average, increased 2-fold (P < 0.01) in cells from insulin resistant patients compared with normal cells. Finally, in downregulated cells from obese and obese diabetic patients, the recycling of the internalized insulin receptor was completely disrupted. In conclusion, monocytes from obese patients with and without Type 2 diabetes mellitus, present increased intracellular insulin concentrations and these conditions are associated with a significant impairment of insulin receptor processing. Increased intracellular insulin concentration in cells from these patients may be necessary in order to overcome insulin resistance.
Asunto(s)
Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus/sangre , Hiperinsulinismo/sangre , Insulina/sangre , Monocitos/metabolismo , Obesidad/sangre , Cromatografía Líquida de Alta Presión , Humanos , Hiperinsulinismo/etiología , Membranas Intracelulares/metabolismo , Persona de Mediana Edad , Concentración Osmolar , Receptor de Insulina/metabolismoRESUMEN
In a group of 46 consecutive outpatients attending the diabetic clinic of our Metabolic Department, 30 insulin-dependent and 16 non-insulin-dependent diabetic patients in stable metabolic control, and in 38 age-matched controls, we measured vibration perception threshold with biothesiometer and autonomic function, by means of the five classical cardiovascular tests: R-R interval variations during deep breathing, Valsalva ratio, lying-to-standing, postural hypotension, and sustained handgrip. None of the patients complained of symptoms related to diabetic autonomic neuropathy (DAN) or sensory polyneuropathy. Vibration perception threshold positively correlated with Valsalva ratio (p < 0.05) and deep breathing (p < 0.01), and all of them correlated with age (p < 0.001), but not with duration of diabetes and metabolic control. Patients scored significantly lower than controls in vibration perception threshold and all of the autonomic function tests. According to the outcomes of cardiovascular tests ["Autonomic Score" (AS)] patients were divided into two different groups: presence (DAN+ = AS > or = 3) or absence (DAN- = AS < 3) of autonomic neuropathy. The DAN- group (n = 28, 60.9%) showed no significant differences from the DAN+ group (n = 18, 39.1%) in age, duration of diabetes, glycated hemoglobin, or body mass index. DAN+ patients had vibration perception threshold measured at the first toe tip and at external malleolus significantly higher than DAN- patients (p < 0.01 and p < 0.001, respectively) and controls (p < 0.005), as well as all the other cardiovascular tests except sustained handgrip. No difference in any of these items was observed between DAN- patients and controls.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Sistema Nervioso Autónomo/fisiopatología , Sistema Cardiovascular/fisiopatología , Diabetes Mellitus Tipo 1/fisiopatología , Diabetes Mellitus Tipo 2/fisiopatología , Neuropatías Diabéticas/fisiopatología , Neuronas Aferentes/fisiología , Adulto , Índice de Masa Corporal , Neuropatías Diabéticas/diagnóstico , Femenino , Hemoglobina Glucada/análisis , Humanos , Masculino , Persona de Mediana Edad , Respiración , Umbral Sensorial , Maniobra de Valsalva , VibraciónRESUMEN
This study evaluates the prevalence of diabetes mellitus (DM) in Pisa (Tuscany, Italy) using four independent data sources. The main source, represented by computerized prescriptions for anti-diabetic agents collected over a 4-month period, was validated using three secondary sources: (a) the list of diabetic patients who receive material of self-care from the National Health Service; (b) the clinical records of diabetic patients obtained from a random sample of family doctors; (c) the clinical records of diabetic patients attending our outpatient clinic. The main source provided 3806 patients, and 697 patients were added from the secondary sources, thus identifying a total number of 4503. The prevalence of known DM in the "Pisa area" exclusively reckoned by the main source, was 2.01%, and the prevalence corrected by the addition of the various sources resulted in 2.4%. The capture-recapture method showed a completeness of ascertainment of the survey of 90.1%, and thus an estimated prevalence of known diabetes of 2.64%. Of these, 141 patients had insulin-dependent diabetes mellitus (IDDM) corresponding to 3.2% of identified diabetic subjects (prevalence 0.07% inhabitants); 4362 patients had non-insulin-dependent diabetes mellitus (NIDDM), 96.8% of identified diabetic subjects (prevalence 2.36%). Of patients with NIDDM 10.5% was treated by diet, 65% with oral hypoglycaemic agents (OHA), 23% with insulin and 1.5% with insulin plus OHA. This study shows that the method used in this survey is suitable for epidemiological studies because it does not demand the cooperation of the diabetic patients, is addressed to the entire diabetic population without age discrimination and singles out the diabetic population in a very reliable way.
Asunto(s)
Diabetes Mellitus/epidemiología , Prescripciones de Medicamentos/estadística & datos numéricos , Adulto , Factores de Edad , Edad de Inicio , Anciano , Instituciones de Atención Ambulatoria , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 2/dietoterapia , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , Medicina Familiar y Comunitaria , Femenino , Humanos , Insulina/uso terapéutico , Italia/epidemiología , Masculino , Obesidad , Prevalencia , Factores SexualesRESUMEN
This study retrospectively evaluated two groups of pregnant women. Group A women (n=1,338) were universally screened for gestational diabetes mellitus (GDM) and GDM patients were intensively treated. In Group B (n=4,035), screening was performed only in women at high risk for GDM and treatment was conventional. This study confirms the validity of a cost-effective screening program for the diagnosis of GDM and that selective screening may be an option only in a situation where healthcare resources are very scarce and/or universal screening of any kind is not feasible. Once the diagnosis of GDM has been made, metabolic management with an intensive approach is important to reduce maternal and fetal morbidity. Diagnosis of GDM and intensive treatment represent a cost for the public health system, but permit a significant monetary savings in terms of costs linked to maternal and neonatal morbidity.
Asunto(s)
Diabetes Gestacional/diagnóstico , Diabetes Gestacional/tratamiento farmacológico , Costos de la Atención en Salud , Tamizaje Masivo/economía , Adulto , Análisis Costo-Beneficio , Diabetes Gestacional/metabolismo , Femenino , Humanos , Italia , Embarazo , Estudios RetrospectivosRESUMEN
Plasma amino acid concentrations and metformin levels were measured by high-performance liquid chromatography in a group of diabetic patients on therapy with the biguanide drug. Diabetic patients treated with metformin showed higher concentrations of plasma glutamate, asparagine, alanine, methionine and tryptophan, and lower levels of ornithine in comparison with normal subjects, and higher levels of alanine when compared to diet-treated diabetic patients. No correlation emerged between amino acid concentrations and metformin dose or plasma concentration. It is concluded that besides the various metabolic abnormalities that are known to occur during metformin treatment, patients on therapy with metformin also show multiple changes of plasma amino acid pattern.
Asunto(s)
Aminoácidos/sangre , Diabetes Mellitus Tipo 2/sangre , Metformina/uso terapéutico , Anciano , Cromatografía Líquida de Alta Presión/métodos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Metformina/sangre , Metformina/farmacología , Persona de Mediana Edad , Valores de ReferenciaRESUMEN
This report describes the efficacy of biosynthetic human insulin (BHI) in long-term (one year) therapy of type I diabetic patients previously treated with conventional insulins. The results were compared with those obtained in a group of diabetic patients kept on their usual treatment. In the latter, fasting plasma glucose, HbA1, insulin dose and relative proportions of insulin formulations remained constant throughout the study. In patients switched to BHI, hypoglycaemic episodes occurred during the first week of treatment and fasting plasma glucose was higher than basally at the first two visits (7th and 30th days). Both hypoglycaemia and high fasting plasma glucose were avoided by reducing the amount of short-acting insulin and increasing that of intermediate-acting insulin, so that the short-acting/intermediate-acting insulin ratio was significantly lower during BHI therapy, although the total daily insulin dose remained unchanged. HbA1 levels remained fairly constant throughout the study. It was concluded that in order to achieve full clinical efficacy of BHI, it is important to modify the proportions of short- and intermediate-acting insulin preparations accurately when switching patients from conventional insulin to biosynthetic human insulin.
Asunto(s)
Diabetes Mellitus Tipo 1/tratamiento farmacológico , Insulina/uso terapéutico , Proteínas Recombinantes/uso terapéutico , Adulto , Glucemia/metabolismo , Esquema de Medicación , Femenino , Humanos , Insulina/administración & dosificación , Masculino , Proteínas Recombinantes/administración & dosificaciónRESUMEN
This retrospective study investigates the clinical characteristics of gestational diabetes mellitus (GDM) (time of diagnosis, different treatment, metabolic parameters, etc.) in relation to prepregnancy body mass index (BMI) and the influence of BMI on neonatal outcome. 93 GDM women and 110 control subjects were divided into three groups in relation to their prepregnancy BMI: normalweight (Nw), overweight (Ow) and obese (Ob). GDM was diagnosed significantly (p < 0.01) earlier in Ow and Ob than in Nw. Preterm deliveries and cesarean sections resulted significantly (p < 0.01) increased in all BMI categories of GDM respect to matched controls. Prevalence of neonatal macrosomia was higher in GDM patients (44.6%) compared with normal controls (15.4%) and correlated (p < 0.01) with prepregnancy BMI in both groups. Nevertheless in each BMI category the prevalence of macrosomia was significantly higher in GDM patients. The body weight increase during pregnancy was not associated with neonatal macrosomia. This study shows that prepregnancy BMI is an important risk factor for GDM and is predictive for macrosomia specially in women suffering from GDM.