Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pre-mixed insulin preparations are being used increasingly in the management of children with IDDM. Recently this form of insulin has been produced in a disposable insulin pen device. An open randomized 3-month crossover study was conducted to compare glycaemic control on a self-titrating insulin regimen with a pre-mixed (30:70) preparation, both given twice daily. The pre-mixed preparation was delivered by disposable pen. Forty children (age range 7-16 yr) entered the study. Mean +/- SEM glycosylated haemoglobin (HbA1 %) at the start of the study (13.1 +/- 0.6) compared with values at the end of the self-titrating (11.8 +/- 0.5) and pre-mixed periods (12.5 +/- 0.5), as well as blood glucose profiles taken at 3-weekly intervals, showed no significant change. Fourteen of the children were on insulin ratios other than 30:70 (range 10:90 to 50:50) and were unaffected by the switch (HbA1 at the start of the study 12.7 +/- 1; at the end of the self-titrating 11.5 +/- 0.8; and pre-mixed period 12.5 +/- 0.8). Twenty-one children continued on the pen for a further 12 months with no deterioration in control (HbA1 at the beginning and end of this period being 11.9 +/- 0.7 and 11.0 +/- 0.7, respectively). The children (95%) preferred the disposable pen and pre-mixed insulin regimen. Switching to pre-mixed insulin, while not improving, has no detrimental effect on glycaemic control.
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PMID:Pre-mixed insulin delivered by disposable pen in the management of children with diabetes. 830 95

To characterize its insulin-antagonistic effect, growth hormone (GH) was infused at variable rates (24, 12 or 6 mU kg-1 min-1) for 1 h in 7 IDDM patients. Saline infusion was used as control (C) and all patients participated in all studies. The effect of insulin was measured with the euglycaemic clamp technique for 6 h combined with d-(3-3H)-glucose to evaluate glucose turnover. The insulin levels during the clamps were similar in all studies (23 +/- 3 mU l-1). The infusions produced peak GH levels of (24 rate = 24) 157 +/- 11, (12 rate = 12) 76 +/- 7, and (6 rate = 6) 45 +/- 8 mU l-1 (mean +/- SEM). The insulin-antagonistic effect of GH on glucose uptake was seen after 2 h and was at a maximum 4 to 5 h after the start of the GH infusion (difference in glucose infusion rate between C and 24 was 1.7 +/- 0.4 mg kg-1 min-1, p < 0.01). The resistance was due to a less pronounced effect of insulin to both inhibit rate of appearance and to stimulate rate of disappearance. Infusion of GH at 12 mU kg-1 min-1 induced a less pronounced insulin resistance both with regards to maximal effect (glucose infusion rate C - GH 1.4 +/- 0.5 mg kg-1 min-1, p < 0.05) and duration (3 h). At 6 mU kg-1 min-1, a clear GH-induced insulin-antagonistic effect was only seen during the third hour of the clamp (glucose infusion rate C-GH 1.3 +/- 0.5 mg kg-1 min-1, p < 0.05). GH infusion impaired the effect of insulin to lower both the levels of free fatty acids (NEFA) and glycerol between 2 and 5 h after the start of the infusion (NEFA, C:110 +/- 29, 24:303 +/- 95, p < 0.05: glycerol, C:32 +/- 4, 24:50 +/- 7 mumol l-1, p < 0.05). The present study therefore demonstrates that the insulin-antagonistic effect of GH in IDDM is related to the plasma levels both with regard to duration and response. The results also indicate that GH impairs the effect of insulin on lipolysis in IDDM after physiological peaks.
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PMID:Characterization of the insulin-antagonistic effect of growth hormone in insulin-dependent diabetes mellitus. 858 32

Amylin has been reported to decrease glycogen storage in rodent skeletal muscles and produce insulin resistance in intact rats. To test the acute effect of a human amylin analog (AC137) on glucose metabolism in man, seven IDDM patients were infused in a randomized, double blind, cross-over study with AC137 (100 micrograms/h, n = 1; 50 micrograms/h, n = 6) or placebo for 330 min during a two-step euglycemic clamp (insulin infusion rates, 0.2 and 0.6 mU/kg.min; basal and hyperinsulinemic period, respectively) followed by a hyperinsulinemic hypoglycemic clamp (insulin infusion rate, 1.5 mU/kg.min; hypoglycemic period). During euglycemia, no differences were found in glucose disposal (step 1, 2.43 +/- 0.20 vs. 2.03 +/- 0.26; step 2, 4.28 +/- 0.54 vs. 4.11 +/- 0.45 mg/kg.min; AC137 vs. placebo, mean +/- SEM), arteriovenous substrate balances across the forearm, or hepatic glucose production. During hypoglycemia, glucose fluxes were also similar. However, lactate release from the forearm was more pronounced (P < 0.05) with the analog than with placebo (area under the curve, -11.2 +/- 4.6 vs. -1.4 +/- 2.2 mmol/min.L). Despite similar plasma glucose nadirs (2.7 +/- 0.0 vs. 2.6 +/- 0.1 mmol/L; AC137 vs. placebo), circulating cortisol and GH rose to significantly higher levels during hypoglycemia with the amylin analog (P < 0.05). In conclusion, acute administration of the amylin analog AC137 did not influence insulin-stimulated glucose metabolism during euglycemic conditions. During imposed hypoglycemia, lactate release from skeletal muscle was, however, enhanced, and the rise in cortisol and GH was augmented.
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PMID:Acute effects of the human amylin analog AC137 on basal and insulin-stimulated euglycemic and hypoglycemic fuel metabolism in patients with insulin-dependent diabetes mellitus. 877 80

Normolipidaemic insulin-dependent diabetic (IDDM) patients are characterized by an increase in the smaller VLDL particles, considered to be the most atherogenic. Since blood glucose control is one of the main regulators of lipid metabolism in diabetic patients, it could influence the shift in the distribution of VLDL subfractions towards smaller particles. To evaluate this possibility, VLDL subfractions, post-heparin lipoprotein lipase and hepatic lipase activities have been evaluated in male IDDM patients with either unsatisfactory blood glucose control (group 1, HbA1c > 8%, n = 18) or good blood glucose control (group 2, HbA1c < 8%, n = 16) and in 16 normoglycaemic individuals. The three groups were comparable for sex, age, body mass index, and plasma lipid levels. Three VLDL subfractions (large, Svedberg flotation unit (Sf) 175-400; intermediate, Sf 100-175; small, Sf 20-100) were separated by density gradient ultracentrifugation and analysed for cholesterol, triglyceride, and phospholipid levels. When compared to control subjects both groups of IDDM patients showed a clear shift in VLDL subfraction distribution with a significant increase in the proportion of small VLDL (group 1; 49 +/- 2%; p < 0.005; group 2: 51 +/- 3%, p < 0.01; control subjects 40 +/- 2%) (mean +/- SEM) in relation to total VLDL. By contrast, the absolute lipid concentration of small VLDL was higher only in group 1, compared to control subjects (35 +/- 4 vs 27 +/- 3 mg/dl, p = 0.05). Post-heparin hepatic lipase activity was significantly reduced in both IDDM groups (group 1: 254 +/- 19 mU/ml, p < 0.05; group 2: 202 +/- 19 mU/ml, p < 0.005; control subjects 317 +/- 31 mU/ml). In conclusion, normolipidaemic IDDM patients show an increase in the smallest VLDL, whatever their degree of blood glucose control. However, this abnormality may be clinically relevant only in patients with unsatisfactory blood glucose control, since absolute lipid concentration of these potentially atherogenic particles is only increased in this group.
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PMID:Very low density lipoprotein subfraction abnormalities in IDDM patients: any effect of blood glucose control? 878 15

The purpose of our study was to determine the Doppler ultrasound characteristics of fetal breathing-related nasal fluid flow velocity in pregnancies complicated by diabetes mellitus and to examine any changes in the timing parameters of fetal breath cycle relative to maternal blood glucose level. Fetal nasal fluid flow velocity was studied in 67 women at 30-41 weeks of gestation. In 37 cases, the pregnancy was uncomplicated; in 13 cases, the pregnancy was complicated by type I diabetes mellitus; and in 17 cases, the pregnancy was complicated by gestational diabetes. At the examination, subjects with diabetes mellitus were grouped by glucose control (normoglycemic and hyperglycemic) and by gestational age: 30-36 weeks and 37-41 weeks. Maternal hyperglycemia was defined as a plasma glucose value ranging from 140 to 205 mg per 100 ml. A continuous videotape record of the spectral Doppler imaging of fluid flow velocity in the nose was made during each study session. Based on a sample of 25 consecutive fetal breaths, the timing components of breath cycles were determined: time of inspiration (Ti), time of expiration (Te), breath-to-breath interval (Ttotal), and ratio of Ti and Te (Ti/Te). There was a statistically significant difference between the Ttotal (msec) at 30-36 weeks' gestation in the cases of diabetes mellitus with maternal normoglycemia (1,050 +/- 68 SEM) and uncomplicated pregnancy with maternal normal carbohydrate intolerance (1,221 +/- 52). There was a similar difference in the values of Te (552 +/- 37 and 660 +/- 29, respectively) at 30-36 weeks. In cases of maternal hyperglycemia at 30-36 weeks' gestation, the value of Te (689 +/- 84) was significantly higher than in cases of normoglycemia (552 +/- 37). At 37-41 weeks' gestation, only the fetal Ti/Te ratio in normoglycemic diabetic patients was significantly lower than in an uncomplicated pregnancy. No differences were found in the other timing parameters at this gestational age group in cases of diabetes mellitus relative to maternal blood glucose level. No relationship was found between the value of maternal blood glucose and either fetal Ttotal (r2 = 0.003), or Ti/Te ratio (r2 = 0.0001) in cases of diabetes mellitus. Expiratory phase of fetal breath cycle even in well-controlled normoglycemic diabetic women, is significantly shorter than in uncomplicated pregnancies before 37 weeks of gestation. Maternal hyperglycemia in these cases prolonged the duration of expiratory phase of fetal breath cycle and significantly decreased the Ti/Te ratio more than 15% at 30-36 weeks of gestation. It is suggested that blood glucose level is involved in the regulation of fetal respiratory center in pregnancies complicated by diabetes mellitus.
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PMID:Doppler ultrasound characteristics of fetal nasal flow in pregnancies complicated by diabetes mellitus. 879 95

This study is based on the hypothesis that endothelins (ETs), which are 21-amino acid peptides with vasoactive and proliferative properties, could be implicated in the development of complications of insulin dependent diabetes mellitus (IDDM) in children and adolescents. We determined plasma ET 1-21 concentrations by radioimmunoassay in 59 patients with IDDM (32 male, 27 female) and in 41 healthy siblings (20 male, 21 female) and investigated the association of ET 1-21 concentrations with age, sex, control of diabetes (expressed as % of glycosylated hemoglobin), duration of disease and presence of complications. Plasma ET 1-21 concentrations (mean +/- SEM) were 14.12 +/- 0.30 pg/ml in IDDM and 15.34 +/- 0.47 pg/ml in healthy siblings. The difference was statistically significant (p = 0.01) after controlling for age and sex by multiple logistic regression. In the group with IDDM, analysis of covariance showed duration of disease to be the only variable associated with ET 1-21 values (b = 0.2179 pg/ml/yr, p = 0.04). It is concluded that in youngsters with IDDM ET plasma concentrations are lower than in healthy controls, negatively associated with duration of the disease and not directly implicated in diabetic angiopathy.
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PMID:Endothelin 1-21 plasma concentrations in children and adolescents with insulin-dependent diabetes mellitus. 891 Aug 15

Autonomic dysfunction in insulin-dependent diabetic (IDDM) patients has been associated with abnormalities of left ventricular function and an increased risk of sudden death. A group of 30 patients with IDDM and 30 age, sex and blood pressure matched control subjects underwent traditional tests of autonomic function. In addition, baroreceptor-cardiac reflex sensitivity (BRS) was assessed using time domain (sequence) analysis of systolic blood pressure and pulse interval data recorded non-invasively using the Finapres beat-to-beat blood pressure recording system. 'Up BRS' sequences-increases in systolic blood pressure associated with lengthening of R-R interval, and 'down BRS' sequences-decreases in systolic blood pressure associated with shortening of R-R interval were identified and BRS calculated from the regression of systolic blood pressure on R-R interval for all sequences. We also assessed heart rate variability using power spectral analysis and, after expressing components of the spectrum in normalised units, assessed sympathovagal balance from the ratio of low to high frequency powers. IDDM subjects underwent 2-D echocardiography to assess left ventricular mass index. Standard tests of autonomic function revealed no differences between IDDM patients and control subjects, but dramatic reductions in baroreceptor-cardiac reflex sensitivity were detected in IDDM patients. 'Up BRS' when supine was 11.2 +/- 1.5 ms/mmHg (mean +/- SEM) compared with 20.4 +/- 1.95 in control subjects (p < 0.003) and when standing was 4.1 +/- 1.9 vs 7.6 +/- 2.7 ms/mmHg (p < 0.001). Down BRS when supine was 11.5 +/- 1.2 vs 22 +/- 2.6 (p < 0.001) and standing was 4.4 +/- 1.9 vs 7.3 +/- 2.5 ms/mmHg (p < 0.003). There were significant relations between impairment of the baroreflex and duration of diabetes (p < 0.001) and poor glycaemic control (p < 0.001). From a fast Fourier transformation of supine heart rate data and using a band width of 0.05-0.15 Hz as low-frequency and 0.2-0.35 Hz as high frequency total spectral power of R-R interval variability was significantly reduced in the IDDM group for both low-frequency (473 +/- 62.8 vs 746.6 +/- 77.6 ms2 p = 0.002) and high frequency bands 125.2 +/- 12.9 vs 459.3 +/- 89.8 ms2 p < 0.0001. When the absolute powers were expressed in normalised units the ratio of low frequency to high frequency power (a measure of sympathovagal balance) was significantly increased in the IDDM group (2.9 +/- 0.53 vs 4.6 +/- 0.55, p < 0.002 supine: 3.8 +/- 0.49 vs 6.6 +/- 0.55, p < 0.001 standing). Thus, time domain analysis of baroreceptor-cardiac reflex sensitivity detects autonomic dysfunction more frequently in IDDM patients than conventional tests. Impaired BRS is associated with an increased left ventricular mass index and this abnormality may have a role in the increased incidence of sudden death seen in young IDDM patients.
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PMID:Assessment of baroreceptor-cardiac reflex sensitivity using time domain analysis in patients with IDDM and the relation to left ventricular mass index. 893 9

Fibroblast growth factor-2 (FGF-2) is a potent mitogen and angiogenic factor normally absent from the adult circulation. We have previously shown that it appears in normal maternal serum and that circulating FGF-2 levels are elevated in pregnancies complicated by diabetes. This study was performed to determine whether serum FGF-2 is more abundant in pregnant diabetic women with retinopathy than in those without. Serum was collected monthly between 14-30 weeks gestation and every 2 weeks from then until delivery (35-38 weeks) from 36 women with type 1 diabetes. FGF-2 was extracted by heparin-Sepharose affinity chromatography and quantified by specific RIA. Patients were divided according to the White classification of diabetes. In 17 women without retinopathy (White groups B, C, and D0), immunoreactive FGF-2 was detectable at 14 weeks (mean +/- SEM, 154 +/- 39 pmol/L), was maximal after 26 weeks (306 +/- 38 pmol/L), after which values steadily declined to term (212 +/- 48 pmol/L). In 19 women with simplex or proliferative retinopathy (White groups D+ and R), circulating levels of FGF-2 were significantly greater between 22-32 weeks gestation (22 weeks, 480 +/- 102 vs. 239 +/- 38 pmol/L; P < 0.05). Serum FGF-2 was significantly correlated with hemoglobin A1c levels at 22, 30, and 34 weeks gestation. The mean birth weight of the infants did not significantly differ between groups. Macroalbuminuria was absent in all patients, and creatinine clearance and blood pressure did not significantly differ between the two groups. The results suggest that serum FGF-2 is substantially elevated in pregnant diabetic women with retinopathy in second and early third trimesters. It is unlikely that in these patients this was primarily due to altered FGF-2 clearance, but may relate to excessive production by the utero-placental compartment. The high circulating levels of FGF-2 may be causally related to the development of diabetic retinopathy.
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PMID:Increased levels of serum fibroblast growth factor-2 in diabetic pregnant women with retinopathy. 914 32

Fifteen out-patients with type I diabetes mellitus and microalbuminuria (mean +/- SEM: 95.4 +/- 13.9 micrograms/min), were administered the glycosaminoglycan sulodexide, with the aim of investigating its influence on the rate of albumin excretion. Sulodexide was given intramuscularly in a dose of 600 lipoproteinlipase releasing units/day for three weeks. Albumin excretion was measured before dosing, at weekly intervals during dosing and also during the subsequent follow-up period of six weeks. Sulodexide yielded a clear-cut and statistically significant lowering of albumin excretion after the first week of treatment (from 95.4 +/- 13.9 micrograms/min to 53.6 +/- 11.1 micrograms/min; p = 0.0055); albumin excretion was further decreased after three weeks of treatment (26.5 +/- 6.05 micrograms/min; p = 0.0007) and was maintained during the follow-up period, at the end of which the mean value was still significantly lower than at baseline (39.6 +/- 10.3 micrograms/min; p = 0.01). Sulodexide short-term administration did not influence the routine haematological, haematochemical and coagulative tests performed contemporaneously. Patients' compliance with treatment was very good and no adverse events were reported.
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PMID:A pilot study of the effect of the glycosaminoglycan sulodexide on microalbuminuria in type I diabetic patients. 916 56

Excessive production and deposition of extracellular matrix proteins are characteristic features of diabetic nephropathy. This study tests the hypothesis that cells from diabetic patients who develop nephropathy have a disturbance in collagen metabolism compared with cells from diabetic patients without complications. Kinetics of overall collagen metabolism and total protein synthesis were examined in serially passaged, subconfluent, quiescent skin fibroblasts cultured in either normal (5 mM) or high (25 mM) glucose concentrations from 14 insulin-dependent diabetic (IDDM) patients with nephropathy; 14 IDDM patients without nephropathy matched for age, diabetes duration, and body mass index; and 14 healthy subjects. Fibroblasts were incubated in the presence of 2 microCi/ml [3H]proline, and after labeling the incorporation of [3H]proline into total protein, collagen (collagenase-sensitive material), and noncollagen proteins (collagenase-resistant material) was determined at different time points. Collagen degradation was determined in pulse-chase experiments by following the residual collagen-bound radioactivity after incubation for 8 h with 10 microCi/ml [3H]proline. In high glucose concentrations (25 mM), overall collagen synthesis (measured as [3H]proline incorporation into extracellular and intracellular collagenase-sensitive material) was significantly greater in the patients with nephropathy (mean +/- SEM after a 24-h labeling period: 7189 +/- 671 dpm/10(6) cells) than in the patients without (4341 +/- 267 dpm/10(6) cells; P < 0.01) or healthy control subjects (3836 +/- 234 dpm/10(6) cells; P < 0.01). No significant differences were observed in noncollagen protein production or in collagen degradation rates among the three groups of subjects. In the presence of normal glucose concentrations (5 mM), collagen synthesis was lower in all groups studied, but the differences between IDDM patients with nephropathy and those without remained unaltered. These results suggest that long-term cultured fibroblasts derived from diabetic patients with nephropathy exhibit an abnormality in collagen metabolism. Cells from long-standing diabetic patients without nephropathy have normal collagen metabolism. The increased collagen synthesis is likely to be intrinsic to those diabetic patients susceptible to nephropathy and may play an important role in the sclerotic processes that occur in the kidneys, arteries, and heart.
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PMID:Enhanced collagen synthesis in cultured skin fibroblasts from insulin-dependent diabetic patients with nephropathy. 921 63


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