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

We tested the hypothesis that insulin is an independent risk factor for elevated blood pressure. As our model we selected type 1 diabetes with peripheral circulatory hyperinsulinemia induced by sc insulin treatment. In 15 nonobese normoalbuminuric patients with type 1 diabetes (23.7 +/- 0.8 yr old) and in 15 healthy controls matched for age, sex, and body weight, ambulatory blood pressure was recorded over 24 h. The areas under the curve of free insulin (605 +/- 135 vs. 275 +/- 35 pmol/L.h; P = 0.03) and basal plasma epinephrine concentrations were higher (170 +/- 10 vs. 130 +/- 10 pmol/L; P = 0.02), and the basal aldosterone level was lower (220 +/- 40 vs. 410 +/- 50 pmol/L; P = 0.009) in the patients. The nocturnal decline in systolic blood pressure was less pronounced (13 +/- 1 vs. 19 +/- 2 mm Hg; P = 0.007) in the patients. Multivariate adjustment (r2 = 0.75; P = 0.0002) showed an effect of basal plasma epinephrine and norepinephrine levels and body mass index on the mean nocturnal systolic blood pressure, but showed no effect of age, sex, hemoglobin A1c, aldosterone, or, in particular, insulin. We found a blunted nocturnal fall in blood pressure in nonobese, normoalbuminuric type 1 diabetic patients. These patients showed increased adrenomedullary activity, and this predominantly contributed to the blood pressure alterations. We also found hyperinsulinemia in these patients, but, after controlling for covariates, blood pressure was independent of the insulin level.
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PMID:Nocturnal blood pressure elevation is related to adrenomedullary hyperactivity, but not to hyperinsulinemia, in nonobese normoalbuminuric type 1 diabetes. 863 59

Down-regulation of hormonal effects is in the presented simulation related to the number of functional receptors and quantity of available hormonal stimulation. The former is in the model substituted with the quantity of stimulation able to produce a full down-regulation (Hs100) of target cells. The halftime (t1/2) of the hormonal effect recovery means the interval before the second hormonal stimulation can elicit half of the initial hormonal effect. Recovered hormonal effects are calculated after periods of two, three, four and five t1/2. The interval among hormonal stimulations varied from 1/2 to 5/2 of t1/2. Shorter than t1/2 intervals showed profound down-regulation even at weak hormonal stimulations (> 20% of Hs100). Stable levels of hormonal effects after frequent hormonal stimulations are found only in cases of very weak stimulations (< 10% of Hs100). Intervals equalling t1/2 among weak stimulations (< 20% Hs100) produced stable hormonal effects. Further prolongation among repeated stimulations improved stability of hormonal effects and even strong stimulations (> 60% of Hs100) were followed with only temporary profound down-regulation. Hormone-binding receptors unable to activate target cells are in the model described as defective. Probability for the target cell to be stimulated is in the model defined as P. Relative quantity of hormonal stimulation per target cell needed to achieve certain P is calculated for cells bearing different proportions of defective receptors. Activation following weak hormone stimulations is highly probable (> 90%) for cells bearing less than 30% of defective receptors. With the proportion of defective receptors over 60%, the activation probability after weak hormone stimulations is reduced (< 66%). Down-regulation can be considered as a modulator of hormonal effects. In prediabetic patients, intense stimulation of pancreatic insulin secretion by frequent or increased ingestion of carbohydrates might lead to sustained hyperinsulinemia. A substantial portion of the target tissue would become down-regulated with increased number of defective insulin receptors. Poor glucose utilization in the down-regulated tissue with resultant hyperglycemia would further stimulate insulin secretion until failure. Reduced tissue transportability of large hormone molecules, such as hGH, or proinsulin, can make their effects more pronounced in the perivascular space. Circulating hormone binding proteins or the basal membrane thickening in small vessels can further decrease the hormonal effects on more remote cells. Physical activity in IDDM patients increases insulin effect. Possible explanation is that increased muscle perfusion is making more insulin available to the less down-regulated skeletal muscle cells.
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PMID:Computer simulation of factors involved in the down-regulation of hormonal effects. 867 50

Insulin stimulates ob gene expression and increases serum leptin concentrations in mice and in noninsulin-dependent diabetes mellitus patients. Obese women have higher ob gene messenger ribonucleic acid levels than obese men, suggesting that sex hormones are involved in the regulation of leptin synthesis. We studied the relationship among leptin, insulin, and testosterone in 15 men with insulin-dependent diabetes mellitus (IDDM; age, 29 +/- 2 yr; body mass index, 22.7 +/- 0.5 kg/m2; body fat, 9.5 +/- 1.0%; insulin dose, 44 +/- 4 U/day; hemoglobin A1c, 8.1 +/- 0.3%; diabetes duration, 12.7 +/- 2.0 yr) and 15 healthy control subjects (age, 27 +/- 1 yr; body mass index, 22.6 +/- 0.4 kg/m2; body fat, 9.6 +/- 0.5%) in the fasting state. In addition, the effect of a 4-h euglycemic hyperinsulinemia (approximately 600 pmol/L) on the plasma leptin concentration was determined. The fasting leptin concentration was negatively correlated to plasma testosterone (r = -0.55; P < 0.05) in IDDM patients. The fasting plasma leptin level rose 25% in healthy subjects (from 1.0 +/- 0.2 to 1.3 +/- 0.3 ng/mL; P < 0.05). The leptin levels were higher in IDDM subjects (P < 0.01) and remained unchanged (2.7 +/- 0.2 vs. 2.7 +/- 0.2 ng/mL) during hyperinsulinemia. We reached the following conclusions. 1) In nonobese IDDM patients, leptin synthesis is resistant to the acute effect of insulin. 2) Serum testosterone may contribute to the regulation of leptin synthesis in IDDM patients.
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PMID:Leptin synthesis is resistant to acute effects of insulin in insulin-dependent diabetes mellitus patients. 902 22

Type 1 diabetes mellitus is caused by a lack of insulin that results from the autoimmune destruction of the pancreatic beta-cells. Severe diabetes, if not controlled by periodic insulin injections, can lead to ketoacidosis and death. We have previously shown that sustained low level production of insulin in the liver of diabetic rats prevented their death from complications of diabetes. To test the hypothesis that there is a window of serum insulin concentrations that can prevent ketoacidosis without significant risk of hypoglycemia secondary to hyperinsulinemia, rats were infused with various doses of a recombinant retrovirus encoding an engineered rat preproinsulin-1 gene. The gene was engineered to allow processing into mature insulin by the protease furin. At the lower doses tested, fatal ketoacidosis was prevented, but the rats exhibited nonfasting hyperglycemia. At intermediate doses, which resulted in serum insulin concentrations of 1.6 mg/ml, the rats achieved near-normoglycemia and no serum ketones. These rats did not exhibit hypoglycemia even during a 24-h fast. At high virus doses, the animals achieved nonfasting normoglycemia but exhibited hypoglycemia during the fast. In conclusion, we have defined a therapeutic window of hepatic insulin expression that provides protection against ketoacidosis without significant risk of hypoglycemia. This window of sustained hepatic insulin expression might permit its development into a novel treatment modality for the prevention of ketoacidosis in patients with severe insulin-dependent diabetes mellitus.
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PMID:Hepatic insulin gene expression as treatment for type 1 diabetes mellitus in rats. 917 Dec 46

Recent studies at our institution using positron emission tomography (PET) provide evidence that both myocardial blood flow (MBF) and glucose metabolism may be affected in patients with diabetes mellitus. A retrospective study revealed inadequate myocardial glucose uptake as assessed by 2-[18F]fluoro-2-deoxyglucose (18FDG) in 64% of type I (insulin-dependent diabetes mellitus, IDDM) and 36% of type II (non-insulin-dependent diabetes mellitus, NIDDM) patients. However, a study in 7 patients with IDDM and 9 controls showed that metabolic standardization using hyperinsulinemic-euglycemic clamp is associated with similar myocardial glucose uptake in both groups (0.43 +/- 0.16 vs 0.44 +/- 0.12 micromol/g per min; p = nonsignificant). Furthermore, we studied MBF as assessed by [13N]ammonia in 15 IDDM patients without coronary artery disease. We found an impairment in flow reserve in diabetic patients as compared with a control group of 13 healthy volunteers (2.6 +/- 1.3 vs 4.0 +/- 0.6; p <0.01), which was primarily due to a significantly higher resting MBF (95.3 +/- 27.7 vs 69.1 +/- 8.1 mL/100 g per min; p <0.01). Hyperemic flow during adenosine infusion tended to be lower in diabetics, but was not significantly different (236.3 +/- 105.7 vs 273.0 +/- 26.0 mL/100 g per min; p = nonsignificant). Morphologic and functional abnormalities of the coronary microcirculation have been reported in diabetic animals and humans. Furthermore, there is an ongoing controversy regarding the existence of a specific diabetic cardiomyopathy that is not related to epicardial coronary disease. However, few studies have explored the effect of diabetes, hyperinsulinemia, or hyperglycemia on MBF and glucose metabolism in humans. With PET it is possible to perform comprehensive noninvasive studies of various aspects of cardiac function in patients with diabetes mellitus.
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PMID:Myocardial blood flow and glucose metabolism in diabetes mellitus. 929 61

The offspring of mother's with diabetes mellitus during pregnancy are presumed to develop altered glucose homeostasis. We analysed metabolic parameters at birth and glucose tolerance and insulin secretion during oral glucose tolerance tests at 1-9 years of age in 129 children born to mothers with pregestational insulin-dependent diabetes (IDDM) and 69 infants of gestational diabetic mothers. Newborns of IDDM mothers displayed higher insulin (p < 0.001), glucose (p < 0.05), and insulin/glucose ratios (p < 0.002) than newborns of gestational diabetic mothers. During childhood, frequencies of impaired glucose tolerance (IGT) rose in infants of IDDM mothers from 9.4% at 1-4 years to 17.4% at 5-9 years of age, while in children of gestational diabetic mothers an increase from 11.1% up to 20.0% was observed. Offspring of gestational diabetic mothers displayed higher stimulated blood glucose (p < 0.025) than infants of IDDM mothers, while children of IDDM mothers showed higher stimulated insulin (p < 0.025), accompanied by increased fasting and stimulated insulin/glucose ratios (p < 0.05 and p < 0.02, respectively). Stimulated insulin in childhood was positively correlated to insulin at birth (p < 0.05). Furthermore, insulin/glucose ratio in childhood showed a positive correlation to insulin (p < 0.01) and insulin/glucose ratio at birth (p < 0.005). In conclusion, a pathogenetic role of fetal and neonatal hyperinsulinism for the development of IGT in both groups of infants of diabetic mothers is suggested, in particular for early induction of insulin resistance in the offspring of mothers with pregestational IDDM.
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PMID:Glucose tolerance and insulin secretion in children of mothers with pregestational IDDM or gestational diabetes. 930 Feb 47

The impaired glucose tolerance in pregnancy (IGT) represents an important fact in aetiopathogenesis of insulin dependent diabetes mellitus (IDDM) and non insulin dependent diabetes (NIDDM) as well as obesitas and cardiovascular diseases in context with fetal hyperinsulinism. Prospective studies of diabetic mothers newborns are difficult by reason of health controls in different outpatient departments. The aim of this review is to claim a general glucose screening in pregnancy looking on the development of newborns in later life. In present preventive prospects were not used to decrease the morbidity in diabetes, obesitas and cardiovascular diseases without gestational diabetes screening in pregnancy. The neonatal onset and late morbidity is dependent on the quality of maternal glycemia in pregnancy measured by means of glycosylated hemoglobin and insulin the amniotic fluid.
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PMID:[Gestational diabetes--perinatal hyperinsulinism and postnatal developmental disorders]. 934 Sep 71

Exaggerated vasoconstriction and blunted vasodilation of peripheral resistance arteries to various vasoactive agents characterize patients with IDDM. We characterized the hemodynamic effects of insulin in skeletal muscle in patients with IDDM. Muscle blood flow and blood volume were measured basally and during a high-dose insulin infusion (5 mU x kg(-1) x min[-1]) in seven normotensive patients with IDDM (age, 30 +/- 6 years; BMI, 24.5 +/- 2.0 kg/m2; blood pressure, 124 +/- 12/78 +/- 11 mmHg) and nine matched normal subjects, using [15O]H2O, [15O]CO, and positron emission tomography (PET). Whole-body insulin sensitivity was determined using the euglycemic insulin clamp technique. Insulin-stimulated whole-body glucose uptake was significantly lower in the patients with IDDM (45 +/- 15 micromol x kg(-1) x min[-1]) than in the normal subjects (62 +/- 14 micromol x kg(-1) x min[-1]) (P < 0.05). Insulin increased muscle blood flow by 111 +/- 69% above basal from 3.0 +/- 2.0 to 5.8 +/- 3.0 ml x 100 g(-1) muscle x min(-1) (P < 0.005) in the normal subjects, but only by 42 +/- 30% from 2.0 +/- 0.9 to 2.9 +/- 1.4 ml x 100 g(-1) muscle x min(-1) (P < 0.005) in patients with IDDM (P < 0.05 for change in flow in IDDM vs. normal subjects). The calculated muscle vascular resistances were comparable basally, but higher during hyperinsulinemia in the patients with IDDM (37 +/- 17 mmHg x 100 g x min x ml[-1]) than in the normal subjects (16 +/- 7 mmHg x 100 g x min x ml[-l]) (P < 0.05). Muscle blood volume increased significantly by insulin in both groups without any difference between the groups. We conclude that the ability of supraphysiological concentrations of insulin to stimulate muscle blood flow is blunted in patients with IDDM, because of the inability of insulin to stimulate linear flow velocity rather than blood volume in skeletal muscle. This defect adds yet another defect to the list of abnormalities in vascular function in IDDM, which might predispose these patients to develop hypertension.
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PMID:Effects of insulin on blood flow and volume in skeletal muscle of patients with IDDM: studies using [15O]H2O, [15O]CO, and positron emission tomography. 939 89

IDDM patients treated with conventional subcutaneous insulin have an abnormal increase in cholesteryl ester transfer (CET), the proatherogenic step in reverse-cholesterol transport that results in the enrichment of the apolipoprotein (apo) B-containing lipoproteins (VLDL, LDL) with cholesteryl ester (CE). This disturbance is closely linked to iatrogenic hyperinsulinemia and the nonphysiologic stimulation of lipoprotein lipase (LpL), a physiologic activator of CET, because lowering systemic insulin levels by administering insulin through the intraperitoneal insulin route normalizes LpL and CET. Hyperinsulinemia persists in IDDM patients who undergo successful pancreas-kidney transplantation (PKT) when their allografts are placed in the pelvis and drain into the iliac vein. Therefore, to determine whether hyperinsulinemia promotes CET in this setting, we studied CET, LpL, and insulin levels in 14 euglycemic normolipidemic IDDM PKT patients with near-normal kidney function (creatinine 1.5 +/- 0.4 mg/dl). Consistent with our prediction, the net mass of CE transferred from HDL to VLDL + LDL was significantly increased in the PKT group (P < 0.001) compared with nondiabetic renal transplant patients receiving the same immunosuppressive drugs and healthy control subjects. Both basal and arginine-stimulated insulin levels were increased above the kidney transplant group's levels and correlated with the mass of CE transferred at 2 h (r = 0.71, P < 0.05; r = 0.66, P < 0.05, respectively). Total basal LpL activities, LpL and hepatic triacylglycerol lipase activities, and LpL mass all tended to be higher than levels in healthy control subjects. Consistent with these changes in lipase activity, VLDL particle size was significantly reduced (P < 0.025) compared with that of control subjects. These findings indicate that PKT patients with systemically draining allografts have a persisting profile of potentially atherogenic disturbances in insulin levels, LpL, and CET that resemble IDDM patients treated with conventional subcutaneous insulin injections.
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PMID:Alterations in cholesteryl ester transfer, lipoprotein lipase, and lipoprotein composition after combined pancreas-kidney transplantation. 942 83

Turner syndrome afflicts approximately 50 per 100,000 females and is characterized by retarded growth, gonadal dysgenesis, and infertility. Much attention has been focused on growth and growth promoting therapies, while less is known about the natural course of the syndrome, especially in adulthood. We undertook this study to assess the incidence of diseases relevant in the study of Turner syndrome. The study period was from January 1, 1984 to December 31, 1993, and the study base was all women living in Denmark during the study period. We used data from the Danish Cytogenetic Central Register and the Danish National Registry of Patients to assess morbidity. This study supports several earlier studies reporting increased morbidity and confirms results of a recent study on cancer in Turner syndrome. Women with Turner syndrome seem to have an increased incidence of fractures, osteoporotic fractures in adulthood, and non-osteoporotic fractures in childhood. Furthermore, diabetes mellitus, both NIDDM and IDDM, was found with a markedly increased incidence in Turner syndrome, as well as ischemic heart disease, hypertension, and stroke. The risk of cancer, except cancer of the large bowel, does not seem to be elevated in Turner syndrome. Our data suggest that patients with Turner syndrome are extraordinarily prone to abnormalities constituting the metabolic syndrome (e.g., hypertension, dyslipidaemia, NIDDM, obesity, hyperinsulinemia and hyperuricemia). The present data may help to explain the decreased life span found in patients with Turner syndrome.
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PMID:Morbidity in Turner syndrome. 947 75


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