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)

To examine the impact of opiate blockade on glucose counterregulation we performed two hypoglycemic insulin clamp studies with and without naloxone in healthy subjects and well-controlled insulin-dependent (IDDM) patients with defective glucose counterregulation. During both studies plasma glucose fell to 55-60 mg/dl and was then maintained at that level using a variable glucose infusion. In normal subjects, naloxone increased glucose production, thereby reducing the exogenous glucose dose needed to maintain the hypoglycemic plateau. Epinephrine and cortisol responses to hypoglycemia were increased during naloxone plus insulin compared with insulin alone; glucagon responses were unaffected. IDDM patients with suppressed hepatic and hormonal responses to insulin-induced hypoglycemia also demonstrated greater stimulation of glucose production as well as epinephrine, growth hormone, and cortisol release during the naloxone study. In the absence of hypoglycemia, naloxone did not significantly affect glucose production or glucoregulatory hormones. We conclude that opiate blockade augments glucoregulatory responses to insulin-induced hypoglycemia, even in IDDM patients with preexisting defects in glucose counterregulation. This effect is at least in part due to enhanced counterregulatory hormone release during hypoglycemia. Endogenous opiates may modulate hormonal responses during hypoglycemia; their blockade could provide a means of ameliorating defective counterregulation in IDDM patients.
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PMID:Opiate blockade enhances hypoglycemic counterregulation in normal and insulin-dependent diabetic subjects. 205 61

To investigate whether cell-mediated immunity against the adrenal medulla occurs in type I diabetes (IDDM), we conducted a retrospective autopsy study of adrenal glands from IDDM and nondiabetic subjects using formalin-fixed tissue. Forty-four IDDM subjects, aged 4-67 yrs (mean +/- SD, 44.8 +/- 15.4) with a duration of IDDM from 0-55 yr (28.6 +/- 14.2), and 29 nondiabetic controls, aged 8-82 yr (51.8 +/- 18.6), were evaluated for a lymphocytic infiltrate using UCHL1, which recognizes a subpopulation of resting T-lymphocytes and most activated T-lymphocytes. Immunohistochemistry using antihuman B-cell antibody (L26) was also performed. Sections were scored for both lymphocytic infiltrates and fibrosis [none (0), small (1), moderate (2), or large (3)]. Blinded scoring was performed. A moderate to severe UCHL1 infiltrate was present in 9 of 44 (20%) IDDM, compared with 1 of 29 (3%) control subjects (P less than 0.04). Mild to severe fibrosis (score 1, 2, or 3) was present in 22 of 42 (52%) IDDM subjects compared with 4 of 25 (16%) control subjects (P = 0.003). Eight of 42 (19%) IDDM subjects had moderate to severe fibrosis (score 2 or 3) compared with 1 of 25 (4%) control subjects. Seventeen of 44 (39%) IDDM subjects had either a moderate to large cellular infiltrate or moderate to severe adrenal medullary fibrosis compared with 2 of 29 (7%) control subjects (P = 0.003). Staining of the adrenal medulla with L26 revealed a large cellular infiltrate in only one subject who was UCHL1 negative. Adrenal medullitis was observed in 20% of IDDM subjects, suggesting that the adrenal medulla may be another immunological target in IDDM.
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PMID:Adrenal medullitis in type I diabetes. 222 6

Stored sera from 466 patients with insulin-dependent diabetes mellitus and from 144 controls were examined for organ-specific antibodies to human adrenal cortex. Adrenal antibodies were found in seven of the patients with IDDM (1.5%) and in one control (0.7%). None of 91 black patients with IDDM had adrenal antibodies. All of the seven patients with adrenal antibodies had other organ-specific antibodies. Three had clinical hypothyroidism and one was thyrotoxic. All of these seven patients had a HLA-B8-bearing haplotype, suggesting that the B8-bearing haplotype confers an extremely high "relative risk" for adrenal autoimmunity in IDDM. Organ-specific autoimmune disease and/or organ-specific antibodies were found in 30% of the first-degree relatives of these eight probands with the adrenal antibodies (seven with IDDM and one control). We conclude that screening patients with IDDM for adrenal antibodies of low yield (1.9% among white patients). Further, adrenal antibodies may be present for at least two years without the development of Addison disease. Antibodies reactive only to the zona glomerulosa of the adrenal cortex may be benign. Patients with IDDM and thyroid microsomal antibodies are more likely to have adrenal antibodies (6.5%), as are patients with IDDM and a B8-bearing haplotype and those with IDDM and family histories of organ-specific autoimmunity.
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PMID:Adrenal autoantibodies and Addison disease in insulin-dependent diabetes mellitus. 740 Aug 84

Children with long-standing IDDM have impaired counterregulatory responses to hypoglycemia. To determine whether children with new onset IDDM also have altered counterregulation, we studied the counterregulatory responses to hypoglycemia in twenty children with new onset IDDM (5-6 days, age 12.6 +/- 2.9 yr, mean +/- SD), and compared these responses to 47 subjects with long-standing IDDM (duration 7.8 +/- 3.6 yr, age 15.3 +/- 2.5 yr) and 21 controls (age 14.2 +/- 2.8 yr). Six new onset subjects were restudied three months later during their remission. Glucose nadir in new onset (2.7 +/- 0.1 mmol.l-1) was similar to controls (2.4 +/- 0.1 mmol.l-1), but was higher than in long-standing IDDM (2.2 +/- 0.1 mmol.l-1). Both groups of diabetic subjects had lower glucagon responses to hypoglycemia than controls (p < 0.005). Glucagon responses in new and long-standing diabetes did not differ. Epinephrine was diminished in new IDDM compared to controls (p < 0.01). Glucose recovery was faster in new onset than in long-standing IDDM (p < 0.001) and the same as in controls. Responses remained diminished 3 months after diagnosis despite increased C-peptide and lower glycosylated hemoglobin. Thus, children with IDDM have diminished counterregulatory responses to hypoglycemia at diagnosis, that are similar to those in long-standing IDDM. The reasons for this impairment and its clinical application in childhood require further investigation.
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PMID:Impaired counterregulatory hormone responses to hypoglycemia in children and adolescents with new onset IDDM. 782 Feb 18

Abnormal vascular reactivity has been implicated in the aetiology of diabetic microvascular disease and we have previously demonstrated enhanced contractility of hand veins to noradrenaline in insulin-dependent diabetic (IDDM) patients with microalbuminuria. We have now assessed the possible contribution of subclinical peripheral nerve dysfunction to exaggerated vascular reactivity in micro-albuminuric patients. Twenty-five IDDM patients (15 with microalbuminuria), none of whom had symptomatic neuropathy, and 10 control subjects were studied. Vasoconstrictor responses were measured in dorsal hand veins using noradrenaline and phenylephrine. Conduction in median, peroneal and sural nerves was assessed using electrophysiology, and autonomic function using standard cardiovascular reflex tests. The noradrenaline dose causing 50% vasoconstriction was significantly lower in the microalbuminuric diabetic subjects compared with normoalbuminuric (3.6(1.7) mean (SEM) ng/min vs 20.1(6.0) ng/min, p = 0.0002) and non-diabetic subjects (35.1(5.0) ng/min; p < 0.0001). However, reactivity to phenylephrine did not differ between the groups. Median nerve motor conduction velocity was significantly slower in microalbuminuric (48.4(1.4) m/s) than in normoalbuminuric (52.7(1.2) m/s, p = 0.04) and non-diabetic subjects (56.7(0.9) m/s, p = 0.0001). In the diabetic group overall, there was a strongly positive linear correlation between vascular response to noradrenaline and conduction velocity in both the median nerve (r = 0.62, p = 0.0009) and peroneal nerve (r = 0.53, p = 0.006). There was no correlation between phenylephrine-induced responses and motor conduction velocity in either nerve, nor were indices of autonomic function correlated with vascular reactivity to either agent.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Asymptomatic peripheral nerve dysfunction and vascular reactivity in IDDM patients with and without microalbuminuria. 785 85

Metabolically well controlled insulin-dependent diabetic subjects (IDDM) have deficient autonomic adrenomedullary responses to hypoglycemia. This defect, coupled with the characteristic deficient glucagon response to hypoglycemia, predisposes well-controlled IDDM subjects to an increased incidence of severe hypoglycemic episodes. In this report we describe a physically trained subject with long-duration IDDM (9 years) who was rigorously well-controlled (normal HBA1c), yet had exaggerated epinephrine responses to hypoglycemia compared with normal controls. Steady state epinephrine levels during a low-dose insulin (9 pM/kg/min) hypoglycemic clamp (2.9 +/- 0.1 mM) were approximately 2-fold higher compared with normal controls (10.6 vs. 5.5 +/- 0.7 nM). Epinephrine levels during a high-dose insulin (30 pM/kg/min) hypoglycemic clamp (2.8 +/- 0.1 mM) were also increased compared with normal controls (13.1 vs. 8.8 +/- 0.6 nM). We conclude that physical training in this metabolically well-controlled IDDM subject was associated with an augmented autonomic adrenomedullary response to hypoglycemia.
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PMID:Exaggerated epinephrine response to hypoglycemia in a physically fit, well-controlled IDDM subject. 820 Feb 95

Nephropathy commonly develops in patients with insulin-dependent (type 1) diabetes. Administration of an antihypertensive agent to type 1 diabetes patients with microalbuminuria, the first clinically detectable stage of nephropathy, can help slow renal deterioration. It is postulated that the exaggerated vasoconstrictor response to noradrenaline seen in these patients may be relevant in the development of microalbuminuria. This open, non-comparative pilot study was designed to investigate the effects of the alpha-adrenoceptor antagonist doxazosin on noradrenaline-induced hand vein vasoconstriction and on albumin excretion in 14 normotensive type 1 diabetes patients with microalbuminuria. After a three-week placebo run-in period, patients received doxazosin (1, 2, and then 4 mg once-daily, at two-week intervals) for six weeks, followed by a two-week placebo washout period. Vasoconstrictor responses to noradrenaline were measured in dorsal hand veins at the end of each two-week period. Hand vein vasoconstrictor responses to noradrenaline decreased significantly, compared with placebo, at 4 mg/day doxazosin (p = 0.006). The mean albumin excretion rate was lower than baseline at all doses of doxazosin, but changes did not reach statistical significance. Doxazosin was generally well-tolerated; four patients (29%) reported mild-to-moderate treatment-related adverse events. This study indicates that alpha 1-adrenoceptor blockade can blunt the exaggerated vascular reactivity to noradrenaline in normotensive type 1 diabetes patients with microalbuminuria, and supports further research into a potential role for doxazosin in preventing the development of diabetic nephropathy.
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PMID:Hand vein responses to noradrenaline in normotensive patients with insulin-dependent diabetes mellitus and microalbuminuria: effects of alpha-adrenoceptor blockade with doxazosin. 1062 23

In some patients with type 1 diabetes, various physiologic reactions during a cold pressor test (CPT) are impaired. Whether this is caused by diabetic autonomic neuropathy, disturbed secretion of catecholamines, or disturbed blood glucose control is unknown. The authors, therefore, performed CPTs in patients with type 1 diabetes and in control subjects. They measured blood glucose concentrations, insulin concentrations, cardiac autonomic reflexes, and (before and after the CPT) venous catecholamine concentrations and analyzed correlations between these variables. Twenty-two patients with type 1 diabetes (17 men, 5 women; mean age +/- SD, 26.6 +/- 6.5 y; diabetes duration, 7.6 +/- 0.7 y; glycosylated hemoglobin concentration, 7.7 +/- 2.4%) and 35 control subjects with comparable age and gender distributions were studied. Venous catecholamines were measured before and at the end of a 5-minute CPT. In patients with diabetes, only noradrenaline concentrations increased during the CPT, whereas adrenaline concentrations that were already increased at rest did not change. Adrenaline concentrations correlated inversely with insulin concentrations. In control subjects, both adrenaline and noradrenaline increased significantly during the CPT. In both groups, the magnitude of the individual change in catecholamine concentrations was inversely correlated with the respective resting concentration. Changes in catecholamines, cardiovascular reflex tests, and blood glucose concentrations did not correlate with blood pressure changes. The authors conclude that, in patients with diabetes, resting adrenaline concentrations are related to insulin concentrations. Contrary to control subjects, in patients with diabetes, only noradrenaline increased during CPTs. In both groups, changes in catecholamine concentrations after the CPT were inversely related to the respective resting concentrations.
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PMID:Correlates of venous catecholamine concentrations in patients with type 1 diabetes during a cold pressor test. 1095 71

Islet allotransplantation can provide prolonged insulin independence in selected individuals with type 1 diabetes. Whether islet transplantation also restores hypoglycemic counterregulation is unclear. To determine if hypoglycemic counterregulation is restored by islet transplantation, we studied hormone responses and hypoglycemic symptom recognition in seven insulin-independent islet transplant recipients using a 3-h stepped hypoglycemic clamp, and compared their responses to those of nontransplanted type 1 diabetic subjects and nondiabetic control subjects. Glucagon responses of islet transplant recipients to hypoglycemia were significantly less than that observed in control subjects (incremental glucagon [mean +/- SE]: -12 +/- 12 vs. 64 +/- 22 pg/ml, respectively; P < 0.05), and not significantly different from that of nontransplanted type 1 diabetic subjects (-17 +/- 10 pg/ml). Epinephrine responses and symptom recognition were also not restored by islet transplantation (incremental epinephrine [mean +/- SE]: 195 +/- 128 [islet transplant recipients] vs. 238 +/- 73 [type 1 diabetic subjects] vs. 633 +/- 139 pg/ml [nondiabetic control subjects], P < 0.05 vs. control; peak symptom scores: 3.3 +/- 0.9 [islet transplant recipients] vs. 3.1 +/- 1.1 [type 1 diabetic subjects] vs. 6.7 +/- 0.8 [nondiabetic control subjects]). Thus the results indicate that despite providing prolonged insulin independence and near-normal glycemic control in these patients with long-standing type 1 diabetes, hypoglycemic hormonal counterregulation and symptom recognition were not restored by intrahepatic islet transplantation.
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PMID:Intrahepatic islet transplantation in type 1 diabetic patients does not restore hypoglycemic hormonal counterregulation or symptom recognition after insulin independence. 1245 96

mRNA levels of kinin B1 and B2 receptors were determined in HPA axis of type 1 (STZ-induced) and type 2 diabetic rats (ZDF and obese Zucker rats). B2 mRNA levels were elevated in hypothalamus of STZ-induced diabetic (STZ-D) and ZDF rats. Pituitary B2 mRNA levels were elevated in ZDF and obese rats. Adrenal B2 mRNA level was attenuated in STZ-D rats. Kinin B1 receptor may not play a role in HPA axis in diabetes since its expression was unchanged. Enhanced mRNA expression of B2 receptors in hypothalamus of STZ-D and ZDF rats parallels a rise in plasma glucose and reflect a functional relationship. Enhanced pituitary B2 mRNA in type 2 and reduced adrenal in type 1 diabetes account for a differential pattern in release of transmitters.
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PMID:Expression of kinin receptor mRNA in the HPA axis of type 1 and type 2 diabetic rats. 1517 Dec 37


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