Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetes mellitus is accompanied by a variety of alterations in metabolic, cardiovascular, and neuronal function. This paper provides a comprehensive review of the ways in which these pathophysiological aspects of diabetes may impair thermoregulatory function. The influence of diabetic neuropathy and vasculopathy on the control of peripheral blood flow is reviewed and the additional effects of changing levels of blood glucose and insulin are discussed. Both hypoglycaemia and diabetic ketoacidosis are associated with hypothermia, but the reasons for this in ketoacidosis are not clear. Impairment of heat conservation may contribute to and could be a consequence of autonomic neuropathy. The final section of the paper describes a study of our own in which metabolic stability was maintained by infusing insulin intravenously before and during the determination of the thermoregulatory responses to acute cold stress. Under these conditions, there was impairment of reflex vasoconstriction in the limbs of diabetics with neuropathy. This failure to reduce heat loss resulted in half the diabetics with neuropathy shivering in response to moderate cooling, which in some subjects was accompanied by a fall in core temperature. Diabetics without neuropathy and nondiabetics neither shivered nor dropped core temperature.
 ...
PMID:Diabetes mellitus and thermoregulation. 330 96

Controversy has surrounded the role of local hypothermia as a preoperative treatment in amputations of the lower extremity. A study was undertaken to determine the effectiveness of amputation under cryoanesthesia in decreasing postoperative morbidity and mortality in below-knee (BK) amputations. Of 154 BK amputations, only 91 with unreconstructable vascular disease, gangrene, or both, were included in this study. Group I consisted of 48 patients (mean age 63.9 years) who had undergone a routine BK amputation; group II consisted of 43 patients (mean age 65.7 years) who were acutely ill and too unstable to undergo a major surgical procedure. Group II patients were treated by amputation while under cryoanesthesia before any definitive operative intervention. The patients in group II were significantly (p less than 0.05) more ill preoperatively than those in group I. Group II patients had a higher prevalence of previous myocardial infarction, previous stroke, diabetes mellitus, osteomyelitis, and wet gangrene. Seventy percent of the patients in group II had three or more risk factors vs. 46% in group I. Early postoperative mortality rates did not differ significantly between groups (group I, 8%; group II, 9%); the average length of hospital stay for group I patients was 24.2 days compared with 17.7 days in group II. Group II patients sustained slightly more postoperative complications. Amputation under cryoanesthesia appears to be of value in reducing postoperative morbidity and mortality and length of hospital stay in the acutely ill patient with unreconstructable vascular disease, gangrene, or both.
 ...
PMID:Below-knee physiologic cryoanesthesia in the critically ill patient. 334 56

Previous studies have indicated that drug-induced experimental diabetes is associated with increased receptor binding in the rat brain. The purpose of this study was to determine whether the dopamine receptor agonist apomorphine (APO) might produce an accentuated hypothermic response in rats rendered diabetic by alloxan (ALX) treatment. In a previous study, however, the only controls used were ALX-treated rats that failed to develop glycosuria. Therefore, in this study, APO (0.5 mg/kg IP) was administered to ALX-diabetic and non-diabetic as well as saline-treated control rats to ascertain whether the APO responsiveness of ALX-non-diabetic rats was comparable to that of saline control animals. ALX-diabetic rats experienced significantly greater hypothermic response to APO than did the saline control animals. Although ALX-non-diabetic rats were similar to the saline control animals in body weight and blood glucose levels, they too were hyperresponsive to APO. These findings indicate that pancreatic injury from ALX, while not always sufficiently severe to produce overt diabetes, does appear to induce an hyperresponsiveness to APO-induced hypothermia in a manner similar to that observed in severely diabetic animals.
 ...
PMID:Enhanced apomorphine-induced hypothermia in alloxan-treated rats. 337 55

Hypothermia has been reported to be more common in diabetic people than in nondiabetic people, and we have investigated the possibility that autonomic neuropathy may be associated with disordered thermoregulation. After an overnight fast and maintenance of normoglycemia, 12 insulin-treated diabetic patients with and 11 without neuropathy and 12 nondiabetic control subjects, all less than 55 yr, were subjected to external cooling by perfusing water at 16 degrees C through a liquid-conditioned coverall for less than or equal to 45 min. Patients with autonomic neuropathy had impaired vasoconstriction to cooling, particularly in the foot, calf, and forearm. Core temperature rose by 0.2 degrees C in control subjects and by 0.15 degrees C in patients with diabetes but no neuropathy. In contrast, group mean core temperature was unchanged in those with autonomic neuropathy and fell in 3 subjects (P less than .001). Cooling caused shivering in 6 patients with diabetic autonomic neuropathy, but not in those with neuropathy or control subjects (P less than .05). Baseline metabolic rates were similar in all three groups, but the increase after cooling was significantly greater among those who shivered (P less than .05-.02). Thus, young diabetic patients with autonomic neuropathy have impaired thermoregulation to a relatively short period of external cooling, even during metabolic stability, which may predispose to hypothermia.
Diabetes 1988 Jul
PMID:Abnormal thermoregulation in diabetic autonomic neuropathy. 338 91

Since hypothermia is commonly used to lower local and general metabolism during cardiopulmonary bypass, we attempted to identify its specific effects on glucose-insulin interactions. A group of nondiabetic patients undergoing hypothermic (28 degrees C) cardiopulmonary bypass with ischemic (cold) cardiac arrest was compared to a similar group operated on under normothermic conditions with potassium cardioplegia. In the absence of exogenous dextrose administration, hypothermia blocked insulin secretion for the duration of the operation. It also inhibited insulin secretion in response to an exogenous dextrose load (e.g., the priming fluid of the cardiopulmonary bypass circuit) or a glucagon injection, but this inhibition was lifted by rewarming. Blood glucose levels, which during normothermia were mildly elevated even in the absence of dextrose administration, remained normal during the hypothermic phase of cardiopulmonary bypass. By the end of the rewarming period, however, blood glucose levels had reached the same level as observed under normothermic bypass, a fact suggesting that the cold inhibition of hepatic glucose production had been only temporary. Cold inhibition of hepatic glucose production also explains why glucose clearance after a sudden dextrose load was initially faster at low body temperature than at normal temperature. Glucose-clamp studies indicated that insulin resistance was initiated by anesthesia and surgical trauma, and further accentuated by cardiopulmonary bypass, in association with elevated levels of hormones indicative of surgical stress. Regardless of body temperature changes, the assimilation of glucose by nondiabetic subjects during and immediately after bypass called for the infusion of large doses of insulin. A comparison with diabetic subjects showed that insulin-dependent patients (type I diabetes) required no more insulin during cardiopulmonary bypass than normal subjects, whereas patients with type II diabetes exhibited a marked insulin resistance during the operation and in the immediate postoperative period.
 ...
PMID:Glucose-insulin interactions during cardiopulmonary bypass. Hypothermia versus normothermia. 351 20

The high-dose effects of chlorocitrate [(-)-threo-chlorocitric acid] were compared in vivo to another halogenated citrate analog, and a well-known inhibitor of the tricarboxylic acid (TCA) cycle, fluorocitrate. The compounds were given iv to two dogs per sex per group, and a control group received an equimolar amount of citric acid. Chlorocitrate (100 mg/kg) showed TCA cycle inhibition as did fluorocitrate (8 mg/kg) in that both caused depletion of ATP and accumulation of citrate in the liver. Chlorocitrate was a significantly weaker inhibitor of citrate metabolism than fluorocitrate as evidenced by a substantially lower accumulation of serum citrate despite a much higher dose. Both halocitrates produced a similar diabetes-like syndrome (hyperglycemia, glycosuria) mediated by a significant hyperglucagonemia and slight hypoinsulinemia. Chlorocitrate was more potent in this effect and a much greater buildup of plasma lactate ensued (18- versus 3.7-fold increase), enough to explain lethality observed in earlier studies. In contrast, fluorocitrate produced a severe life-threatening hypocalcemia (-30%), and hypercalcuria was observed. This effect on calcium distribution was only minimal with chlorocitrate. Both halocitrates had a similar depressive effect on circulation as evidenced by hypothermia, bradycardia, and elongation of the QT-interval. These changes were considered to be the result of lactic acidosis and the ongoing ion imbalance since heart ATP levels were not depleted.
 ...
PMID:Comparative acute toxicity of chlorocitrate and fluorocitrate in dogs. 359 Jan 93

Blood has a number of rheological properties which partially determine flow, especially at capillary level, and its capacity to deliver oxygen. It is non-Newtonian, pseudoplastic, thixotropic and viscoelastic. Viscosity can be studied with different types of viscosimeters (coaxial cylinder or capillary viscosimeters). It can be defined by the ratio of stress of deformation to rate of deformation. Viscosity depends on macrorheological parameters: hematocrit, serum proteins, especially fibrinogen and globulins, and also on microrheological parameters: degree of aggregation and red blood cell deformability. Viscosity rises when the temperature falls and decreases with the radius of the tube through which the blood flows (Fahraeus-Linqvist effects). Blood viscosity is studied clinically at different temperatures, and, above all, at different rates of deformation by carefully recording the hematocrit. Plasma viscosity, fibrinogen, albumia and immunoglobulin levels, the viscosity of blood cell suspensions in normal saline must also be taken into consideration. Special investigations (rheoscopy, filtrability) provide information about red cell aggregation and deformability. Hyperviscosity syndromes are observed with: --raised hematocrit (polycythemia and pseudopolycythemia), --conditions with raised serum proteins or changes in their composition (especially hyperfibrinogenemia, raised immunoglobulins, low albumin levels); inflammatory syndromes, dysglobulinemias (Fahey's syndrome of plasma hyperviscosity), --low temperature (hypothermia), --increased red cell aggregability (shock, fat embolism), --reduced red cell deformability due to various congenital and acquired conditions (sickle cell anemia, renal failure, hyperlipoproteinemia, thrombosis, diabetes). Conversely, hypoviscosity may occur with a low hematocrit, hypoproteinemia, hypofibrinogenemia, and hyperthermia. Increased viscosity results in a slowing of blood flow, stagnation of its constituents and in ischemia. Therapeutic interventions may be considered on the different components of the hyperviscosity syndrome: hemodilation, plasmapheresis, dispersion of aggregants, agents acting on red cell deformability.
 ...
PMID:[Blood hyperviscosity syndromes. Classification and physiopathological understanding. Therapeutic deductions]. 636 7

We report the occurrence of the adult respiratory distress syndrome (ARDS) in association with uncontrolled diabetes in nine patients. In reviewing the literature we found nine similar cases reported in little over a decade. In most cases no condition known to precipitate ARDS was discovered. The evidence suggests that the severely uncontrolled diabetic state in some way may initiate pathologic events leading to the capillary leak of ARDS. This description of the association of these two entities not commonly recognized as occurring simultaneously has important clinical implications: the entity should be anticipated in uncontrolled diabetic patients who present with acidosis, hypotension, hypothermia, and/or coma. The clinical or radiologic diagnosis of pneumonia or fluid overload should not be made in the uncontrolled diabetic patient in the absence of unequivocal evidence of infection or congestive heart failure. The development of dyspnea, hypoxemia, rales, or infiltrates in the otherwise routine resuscitation of these patients should lead the clinician to suspect the development of ARDS. Prompt invasive monitoring in these cases is indicated to aid in their management and may help to improve survival. We found calculation of the A-a gradient to be useful in patients with uncontrolled diabetes. Although not necessarily predictive, widened gradients were the earliest detectable abnormality found in all patients who developed ARDS.
Diabetes Care
PMID:Adult respiratory distress syndrome complicating severely uncontrolled diabetes mellitus: report of nine cases and a review of the literature. 682 90

Clinical features and specific aspects of treatment were evaluated in 612 patients with gram-negative bacteremia observed over a 10 year period. Coagulation abnormalities or thrombocytopenia were observed in 64 per cent of the patients. Evidence of disseminated intravascular coagulation (DIC) was found in approximately 10 per cent of them but was of sufficient severity to be associated with subcutaneous or visceral bleeding in 3 per cent of them. The frequency of coagulation abnormalities, other than DIC, was greater in patients with more severe underlying disease but DIC occurred with similar frequency irrespective of the severity of underyling host disease. Coagulation abnormalities of all types were associated with increased fatality rates. Hypothermia was noted in 13 per cent of the patients at the onset of bacteremia but was transient and was not associated with increased fatality. Failure to mount a febrile response greater than 99.6 degrees F within the first 24 hours of bacteremia was associated with a significant increase in fatality rates. Prior corticosteroid therapy diminished the febrile response to bacteremia. Age, underlying host disease, granulocytopenia, congestive heart failure, diabetes mellitus, renal insufficiency, nosocomial infections, and antecedent treatment with antibiotics, corticosteroids, and antimetabolites significantly increased fatality rates. Appropriate antibiotic treatment reduced the fatality rate of those with bacteremia by approximately one-half among patients in each category of severity of underlying host disease. In addition, it was shown that early appropriate antibiotic therapy also reduced the frequency with which shock developed by one half. Even after development of shock, appropriate antibiotic therapy significantly reduced fatality rates. The use of combinations of antibiotics could not be demonstrated to significantly improve survival rates. Minimal differences in therapeutic efficacy could be demonstrated between individual antibiotics and various combinations of antimicrobials. Shock occurred in approximately 40 per cent of the patients and its frequency was not influenced by the species of etiologic agent. Contrary to previous reports, corticosteroid therapy in patients with shock did not enhance survival and treatment with an average of 4.0 g/day of hydrocortisone or its equivalents was associated with a significant increase in fatality rates.
 ...
PMID:Gram-negative bacteremia. IV. Re-evaluation of clinical features and treatment in 612 patients. 698 71

Two series of experiments were performed in parallel on the isolated perfused rat pancreas. The experimental conditions differed only as pertaining to temperature. In one series the organ and the perfusion liquid were maintained at 37.5 degrees C and in the other at 28 degrees C. The pancreases were perfused from the start of the experiments with a perfusion medium containing 8.3 mmol/l glucose. The effects of various stimulatory agents were studied (glucose 16.6 mmol/l, tolbutamide 0.4 mmol/l, acetylcholine 0.5 micromole/l, glucagon, 2.8 nmol/l, and L-isoprenaline 0.05 micromole/l). At 37.5 degrees C the insulin secretion induced by high glucose or tolbutamide, acetylcholine, and glucagon was biphasic and not statistically different. In all cases the hypothermia (28 degrees C) decreased insulin secretion. However, glucose-induced and tolbutamide-induced insulin secretion was more decreased than the secretion induced by acetylcholine and glucagon. The study of the secretion ratios obtained at 28 degrees C relative to 37.5 degrees C showed that the ratios for the glucose and tolbutamide groups were significantly lower than those obtained for acetylcholine and glucagon groups for both the first and the second phase. The ratios were not significantly different between glucose and tolbutamide on the one hand and acetylcholine and glucagon on the other hand. In all groups the ratios 28 degrees/37.5 degrees for the second phase were lower than those obtained during the first phase. L-isoprenaline induced only a weak increase in insulin secretion and this was not long lasting; this increase was not statistically different at both temperatures.
Diabetes 1980 Nov
PMID:A different action of hypothermia on insulin release from the isolated, perfused rat pancreas, depending on the stimulating agent. 700 May 86


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>