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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Disruption of intraislet mechanisms could account for the impaired glucagon response to hypoglycemia in type 1 diabetes. However, in contrast to animals, there is conflicting evidence that such mechanisms operate in humans. We have used i.v. tolbutamide (T) (1.7 g bolus + 130 mg/h infusion) to create high portal insulin concentrations and compared this with equivalent hypoglycemia using an i.v. insulin infusion (I) (30 mU/m2 x min). Ten normal subjects underwent two hypoglycemic clamps; mean glucose; I (53 +/- 1 mg/dL); and T (53 +/- 1 mg/dL) (2.9 +/- 0.04 mmol/L vs. 2.9 +/- 0.05 mmol/L), held for 30 min. During hypoglycemia, mean peripheral insulin levels were greater with I (59 +/- 4 mU/L) than T (18 +/- 3 mU/L), P < 0.001. Calculated peak portal insulin concentrations were greater during T (282 +/- 28 mU/L) than I (78 +/- 4 mU/L), P < 0.00005. The demonstration of a reduced glucagon response during T-induced hypoglycemia (111 +/- 8 ng/L vs. 135 +/- 12 ng/L, P < 0.05) with higher portal insulin concentrations suggests that intraislet mechanisms may contribute to the release of glucagon during hypoglycemia in man.
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PMID:The use of tolbutamide-induced hypoglycemia to examine the intraislet role of insulin in mediating glucagon release in normal humans. 914 33

Well-characterized defects in insulin secretion, most notably a loss of glucose-induced insulin secretion, are found in virtually all forms of NIDDM, as well as in early IDDM. Similar abnormalities have been found in all animal models of diabetes in which they have been studied. A novel hypothesis is being proposed to explain the mechanisms responsible for these alterations. Many abnormalities in the various steps of glucose-induced insulin secretion have been identified in rodent models of diabetes, but none by itself seems sufficient to explain the defects. These include a loss of GLUT2, glycogen accumulation, glucose recycling, abnormal glucokinase or hexokinase, altered mitochondrial glycerol phosphate dehydrogenase (mGPDH) activity, abnormal ion channel function and beta cell degranulation. We propose that optimal secretory function is dependent upon the unique differentiation of beta cells that is maintained by a set of transcription factors and that this control is disrupted by the diabetic state. Therefore, we propose that key transcription factors are affected even when beta cells are stressed by insulin resistance in very earliest stages of diabetes and that the abnormality becomes more severe as full-blown diabetes develops, which leads to loss of beta cell differentiation and a resultant derangement of insulin secretion.
Acta Diabetol 1997 Oct
PMID:Transcription factor abnormalities as a cause of beta cell dysfunction in diabetes: a hypothesis. 940 38

The aims of this study were: (1) to estimate the prevalence of insulin-dependent diabetes mellitus (type I) among the population of 0-29-years-old residents in the province of Oristano on 31/12/96; (2) to estimate the incidence of type I diabetes among the population of 0-29-years-old residents in the province of Oristano between 1993 and 1996. Data concerning the cases were collected from two independent sources. The capture-recapture method was utilised to estimate ascertainment probability. Demographic data for the resident population were supplied by 78 communes in the province. The completeness of the primary data source for prevalence was 97.1%; the estimated prevalence was 4.61 per thousand. The number of type I diabetic subjects identified in a population of 60,095 people aged 0-29 years was 276, i.e. a prevalence of 4.59 per thousand (95% confidence intervals [CI] 4.07-5.17). No cases were found in the commune of Arborea, where a large percentage (65%) of immigrants from the Veneto region live (total population < 30 years of age = 1706; 8 expected cases; P < 0.001). The M/F ratio was 1.12. The completeness of primary source of incidence data was 100%. Between 1993 and 1996, the number of new type I diabetic subjects was 86, with a M/F ratio of 1.00. The age-standardised incidence rates were: 54.4 (95% CI 41.3-70.1) in the 0-14-year-age group, 22.0 (95% CI 15.2-30.5) in the 15-29-year-age group and 38.2 (95% CI 31.0-46.4) in the 0-29 year age group, per 100,000 person-years. The incidence and prevalence of type I diabetes mellitus are very high, ranking the province of Oristano among the highest in Europe.
Acta Diabetol 1997 Oct
PMID:Prevalence and 4-year incidence of insulin-dependent diabetes mellitus in the province of Oristano (Sardinia, Italy). 940 41

The study aimed to determine whether a consistent dose-response association can be demonstrated, after adjustment for maternal age and White classification, between glycosylated hemoglobin (HbA1c) values before conception and in the first trimester of pregnancy of insulin-dependent diabetic mothers and adverse fetal outcome (abortions and major malformations). This is a historical follow-up study based on medical records in a geographically defined catchment area. The study comprised 60 pregnancies with HbA1c determinations before pregnancy and 161 with HbA1c in the first trimester in women with type 1 diabetes admitted between 1980 and 1992. Relative risk calculations indicated a highly significant and consistent correlation between HbA1c values above 6.6% and adverse fetal outcome after adjustment for differences in maternal age and White classification. Our data support a clinically significant and consistent relationship between adverse fetal outcome and HbA1c in the first trimester of pregnancy of type 1 mothers, without any indication of a cut-off level below which further improvement in HbA1c was of minor importance.
Acta Diabetol 1997 Oct
PMID:Glycosylated hemoglobin as predictor of adverse fetal outcome in type 1 diabetic pregnancies. 940 44

We assessed the relationship between erythrocyte Na+/H+ antiport activity and myocardial anatomical-functional parameters (by Doppler echocardiography) in normotensive IDDM patients, with and without microalbuminuria. We studied 33 normotensive IDDM subjects and 14 matched healthy controls (group 4). Based on urinary albumin excretion rate (UAER), 23 diabetics were normoalbuminuric, 10 microalbuminuric (group 3). Normoalbuminurics were divided up for normal (group 1, n = 13) or high (group 2, n = 10) antiport activity. We evaluated fasting glycaemia and 24-h urine glucose output, HbA1c, plasma lipids, urea, creatinine and electrolyte clearances, UAER, erythrocyte Na+/H+ countertransport, M-Mode and 2D echocardiograms with Doppler analysis. Antiport, which was higher in diabetics than controls, was significantly overactive in groups 2 and 3 vs group 4, independently from UAER. Diabetics showed left ventricular volume, cardiac mass and systolic function within the control range. In left ventricular diastolic filling, while peak E was similar in diabetic and healthy people, the late peak transmitral flow velocity (peak A) was significantly higher in diabetics than controls, and this was also true in groups 2 and 3 vs group 4. Antiport activity was positively related to peak A (p < 0.03). These observations suggest that (a) the Na+/H+ antiport may be overactive in diabetes, apart from microalbuminuria; (b) increased Na+/H+ antiport activity, in normotensive IDDM people, may be associated with preclinical diastolic myocardial dysfunction ("incipient diabetic cardiomyopathy"?).
Acta Diabetol 1997 Oct
PMID:Erythrocyte Na+/H+ exchange and preclinical abnormalities of the left ventricular diastolic function in normotensive type 1 (insulin-dependent) diabetic patients. 940 45

The effects of insulin-induced hypoglycaemia on the neutrophil respiratory burst were investigated in six patients with type 1 diabetes and six non-diabetic control subjects. Plasma glucose reached similar nadirs in control subjects (0.9 +/- 0.1 mmol 1(-1); mean +/- SEM) and diabetic patients (1.2 +/- 0.2 mmol 1(-1)) (NS). The resting neutrophil respiratory burst was similar in control subjects (1.26 +/- 0.15 mV) and diabetic patients (1.03 +/- 0.18 mV) (NS). The neutrophil respiratory burst fell following hypoglycaemia in control subjects and diabetic patients to 0.38 +/- 0.05 mV (P < 0.001) and 0.54 +/- 0.09 mV (P < 0.05), respectively. This fall was significantly greater in control subjects (ANOVA; P < 0.001). Resting neutrophil counts were not significantly different in control subjects (3.2 +/- 0.3 x 10(9) 1(-1)) and diabetic patients (6.1 +/- 1.5 x 10(9) 1(-1)). Following hypoglycaemia, neutrophil numbers increased in control subjects and diabetic patients to 11.5 +/- 1.4 x 10(9) 1(-1) (P < 0.01) and 9.7 +/- 1.7 x 10(9) 1(-1) (P < 0.05), respectively. This increase was significantly greater in control subjects (ANOVA; P < 0.001). These results suggest that the neutrophil respiratory burst is suppressed in response to hypoglycaemia and that this phenomenon is more pronounced in non-diabetic subjects.
Acta Diabetol 1997 Dec
PMID:Attenuated neutrophil respiratory burst following acute hypoglycaemia in diabetic patients and normal subjects. 945 68

The aim of this study was to determine whether the proportion of circulating B cells expressing the differentiative antigen CD5 was increased in children affected by type 1 diabetes, and whether the number of these cells was correlated with the presence of anti-islet cell autoantibodies. Sixteen children affected by insulin-dependent diabetes mellitus (type 1) were investigated for the presence of B lymphocytes bearing the CD5 surface molecule, T-cell-specific activation markers, organ- and nonorgan-specific autoantibodies. The number of CD5+CD19+ cells was higher in type 1 children with a very recent onset of the disease, as compared with patients on insulin therapy for more than 30 days and controls (P < 0.05). No correlation was found between the number of CD5+CD19+ cells and the presence of either organ- or nonorgan-specific autoantibodies. Our results indicate that CD5+CD19+ cells are involved in the pathogenesis of type 1 diabetes in children. A potential immunoregulatory role of this B cell population is discussed.
Acta Diabetol 1997 Dec
PMID:Increased CD5+CD19+ B lymphocytes at the onset of type 1 diabetes in children. 945 71

To investigate plasma concentrations of lipoprotein(a) [Lp(a)] and apolipoprotein(a) [apo(a)] polymorphism in relation to the presence of microvascular and neurological complications in type 1 diabetes mellitus, 118 young diabetic patients and 127 age-matched controls were recruited. Lp(a) levels were higher in patients than in controls, but the apo(a) isoforms distribution did not differ between the two groups [higher prevalence of isoforms of high relative molecular mass (RMM) in both groups]. Microalbuminuric patients had Lp(a) levels significantly greater than normoalbuminuric patients, and normoalbuminuric patients showed higher Lp(a) levels than controls. Patients with retinopathy or neuropathy showed similar Lp(a) levels to those without retinopathy or neuropathy. No differences in apo(a) isoforms frequencies were observed between subgroups with and without complications (higher prevalence of isoforms of high RMM in every subgroup). However, among patients with retinopathy, those with proliferative retinopathy had higher Lp(a) levels and a different apo(a) isoforms distribution (higher prevalence of isoforms of low RMM) than those with non-proliferative and background retinopathy (higher prevalence of isoforms of high RMM). Our data suggest that young type 1 diabetic patients without microalbuminuria have Lp(a) levels higher than healthy subjects of the same age. Lp(a) levels are further increased in microalbuminuric patients. High Lp(a) levels and apo(a) isoforms of low RMM seem to be associated with the presence of proliferative retinopathy, but have no relation to neuropathy.
Acta Diabetol 1998 Apr
PMID:Lipoprotein(a) levels and apolipoprotein(a) polymorphism in type 1 diabetes mellitus: relationships to microvascular and neurological complications. 962 84

Insulin-dependent diabetes mellitus (type 1) is a common chronic disease of childhood occurring throughout the world. In the literature, its most important determinants include genetic, environmental and familial factors. We evaluated family history as a determinant of the risk of type 1 diabetes mellitus with a population-based case-control study. Information about type 1 patients was taken from the dedicated register of the Abruzzo Region; the register has been collecting incident cases in the age group 0-14 years, diagnosed between 1 January 1990 and 31 December 1996. The control group was taken from the lists of patients attending family pediatricians. The family history data for type 1 and type 2 patients was obtained by a questionnaire, administered to their parents. The risk of type 1 diabetes mellitus associated with its occurrence in first- and second-degree relatives was estimated using logistic regression methods. Our results show that the risk is indeed increased with a positive family history (OR=3.96; 95% CI 1.54-10.14). This shows that the risk of type 1 diabetes mellitus for children whose fathers are affected by the disease is 11 times higher with respect to controls. Moreover, the risk for children whose brothers are affected by the disease is 20 times higher with respect to controls. In contrast, a family history for type 2 diabetes mellitus does not influence the risk.
Acta Diabetol 1998 Apr
PMID:Family history and risk of insulin-dependent diabetes mellitus: a population-based case-control study. 962 91

Hepatocyte growth factor (HGF) is a pleiotropic cytokine known to be involved in tissue regeneration and repair. We measured serum levels of HGF in patients with insulin-dependent diabetes mellitus (type 1). The patients were divided into four groups: (1) 10 patients at clinical presentation before insulin treatment; (2) 19 patients with newly diagnosed type 1 diabetes (diabetes duration 1/2-3 years); (3) 14 patients with long-standing type 1 diabetes without renal involvement (diabetes duration >10 years, and urinary albumin excretion (UAER) <20 microg/ min); and (4) 20 patients with long-standing type I diabetes with renal involvement (diabetes duration >10 years and UAER 20-500 microg/min). Sera from 24 age- and sex-matched healthy blood donors constituted a control group. The HGF levels of the four groups were (mean +/- SD); group 1, 0.74+/-0.14; group 2, 0.78+/-0.40; group 3, 0.86+/-0.42; group 4, 0.79+/-0.27 ng/ml, compared to 0.43+/-0.24 ng/ml in the control group (P<0.0008). HGF levels were not significantly different between the four patient groups. The elevated serum HGF levels did not correlate with complications related to type 1 diabetes, such as UAER, retinopathy and macrovascular complications, suggesting that HGF levels were not associated with the type 1 diabetes complications. In conclusion, our results show that type 1 diabetic patients have increased serum HGF levels compared with controls and that HGF is elevated to the same extent in newly diagnosed as well as in long-standing type 1 diabetes.
Acta Diabetol 1998 Jul
PMID:Elevated hepatocyte growth factor in sera from patients with insulin-dependent diabetes mellitus. 974 58


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