Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The drugs used to treat diabetes mellitus are diverse and involve several classes. However, these drugs can be roughly separated into hypoglycaemic agents, such as insulin and the sulphonylureas, and antihyperglycaemic agents, such as the biguanides, the alpha-glucosidase inhibitors and troglitazone. Reports of insulin overdose are rare. The major effects of insulin overdose are secondary to the insult to the CNS produced by hypoglycaemia. The mainstay of insulin overdose management is glucose replacement therapy. Sulphonylureas are the most commonly used oral antihyperglycaemic agents in the management of type 2 (non-insulin-dependent; NIDDM) diabetes mellitus. Sulphonylureas primarily cause serum glucose reduction by stimulating the release of preformed insulin from the pancreatic islets. The mainstay of sulphonylurea overdose management is glucose replacement therapy, and in severe cases, reduction of insulin release. In the large majority of patients intravenous glucose supplementation will be sufficient to maintain euglycaemia. Repaglinide, a meglitinide analogue, is a new nonsulphonylurea oral hypoglycaemic agent. In overdose, this drug may produce prolonged hypoglycaemia similar to the sulphonylureas. The primary problem with biguanide overdose is the potential for lactic acidosis. The management of biguanide overdose is largely supportive and directed at correcting the metabolic acidosis along with associated complications. The alpha-glucosidase inhibitors, acarbose, voglibose and miglitol competitively and reversibly inhibit the alpha-glucosidase enzymes (glucoamylase, sucrase, maltase and isomaltase) in the brush border in the small intestine, which delays the hydrolysis of complex carbohydrates. They appear unlikely to produce hypoglycaemia in overdose, but abdominal discomfort and diarrhoea may occur. Troglitazone is the first thiazolidinedione antidiabetic drug available. There are no data on overdose, probably because of its very recent introduction. Overdoses with antidiabetic drugs produce major morbidity, with many cases requiring intensive care medicine and prolonged hospital stays. However, fatalities are rare when treatment is initiated early. The management of the hypoglycaemic drugs (insulin and sulphonylureas) is based primarily on restoring and maintaining euglycaemia via intravenous dextrose supplementation. In the case of the sulphonylureas, reduction of insulin secretion via pharmacological intervention may also be necessary. With biguanides the main risk appears to be cardiovascular collapse secondary to profound acidosis. The management focus is on restoring acid-base balance with hyperventilation and the use of insulin to shift the utilisation of glucose from the nonoxidative pathway to the oxidative pathway. Use of haemodialysis has shown equivocal results but may be valuable in metformin overdose.
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PMID:Management of antidiabetic medications in overdose. 982 53

The sleep apnoea/hypopnoea syndrome (SAHS) is characterized by repeated upper airway narrowing or collapse during sleep. The obstruction is caused by the soft palate and/or base of tongue collapsing against the pharyngeal walls because of decreased muscle tone. These episodes are accompanied by hypoxaemia, surges in blood pressure, brief arousal from sleep and pronounced snoring. Individuals with occult disease are at heightened risk of motorway accidents because of excessive sleepiness, sustained hypertension, myocardial infarction, and stroke. The signs and symptoms of SAHS may be recognisable in the dental practice. Common findings in the medical history include daytime sleepiness, snoring, hypertension, and type 2 diabetes mellitus. Common clinical findings include male gender, obesity, increased neck circumference, excessive fat deposition in the palate, tongue (macroglossia) and pharynx, a long soft palate, a small recessive mandible and maxilla, and calcified carotid artery atheromas on panoramic and lateral cephalometric radiographs. Dentists who recognise these signs and symptoms have an opportunity to diagnose patients with occult SAHS. After confirmation of the diagnosis by a physician, dentists can participate in the management of the disorder by fabricating mandibular advancement appliances that enlarge the retroglossal space by anterior displacement of the tongue and performing corrective upper airway surgery that prevents recurrent airway obstruction.
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PMID:Dentistry's role in the diagnosis and co-management of patients with sleep apnoea/hypopnoea syndrome. 1097 58

Profound hypothermia (core temperature of less than 28 degrees C) is a life threatening state and a medical emergency associated with a high mortality rate. The prognosis depends on underlying diseases, advanced or very early age, the duration prior to treatment, the degree of hemodynamic deterioration, and especially, the methods of treatment, including active external or internal rewarming. This is a case study of an 80-year-old female patient with severe accidental hypothermia (core temperature 27 degrees C). She was found in her home lying immobile on the cold floor after a fall. The patient was in a profound coma with cardiocirculatory collapse, and the medical staff treating her was inclined to pronounce her deceased. On her arrival at the hospital, she was resuscitated, put on a respirator and actively warmed. Very severe metabolic disorders were found, including a marked metabolic acidosis composed of diabetic ketoacidosis (she had suffered from insulin treated type 2 diabetes mellitus) and lactic acidosis with a very high anion gap (42) and a hyperosmotic state (blood glucose 1202 mg/dl). There were pathognomonic electrocardiographic abnormalities, J-wave of Osborn and prolonged repolarization. Slow atrial fibrillation with a ventricular response of 30 bpm followed by a nodal rhythm of 12 bpm and reversible cardiac arrest were recorded. The pulse and blood pressure were unobtainable. Despite the successful resuscitation and hemodynamic and cognitive improvement, rhabdomyolysis (CKP 6580 u/L), renal failure and hepatic damage developed. She was extubated and treated with intravenous fluids containing dopamine, bicarbonate, insulin and antibiotics. Her medical condition gradually improved, and she was discharged clear minded, functioning very well and independent. Renal and liver tests returned eventually to normal limits. Progressive bradycardia, hypotension and death due to ventricular fibrillation or asystole commonly occur during severe hypothermia. Respiratory and metabolic, sometimes lactic, acidosis, lethargy and coma, hypercoagulopathy, hyperosmolar state, acute pancreatitis and renal and hepatic failure are frequent complications of hypothermia. Underlying predisposing causes of hypothermia are diabetic ketoacidosis, cerebrovascular disease, mental retardation, hypothyroidism, pituitary and adrenal insufficiency, malnutrition, acute alcoholism, liver damage, hypoglycemia, sepsis, hypothalamic dysfunction, sepsis and polypharmacy, and especially, the use of sedative and narcotic drugs. Our case demonstrates once again that CPR once begun should continue until the successful rewarming because "no one is dead until warm and dead".
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PMID:[Severe accidental hypothermia in an elderly woman]. 1175 73

Sleep is a complex behavioral state that occupies one-third of the human life span. Although viewed as a passive condition, sleep is a highly active and dynamic process. The sleep-related decrease in muscle tone is associated with an increase in resistance to airflow through the upper airway. Partial or complete collapse of the airway during sleep can lead to the occurrence of apneas and hypopneas during sleep that define the syndrome of sleep apnea. Sleep apnea has become pervasive in Western society, affecting approximately 5% of adults in industrialized countries. Given the pandemic of obesity, the prevalence of Type 2 diabetes mellitus and metabolic syndrome has also increased dramatically over the last decade. Although the role of sleep apnea in cardiovascular disease is uncertain, there is a growing body of literature that implicates sleep apnea in the pathogenesis of altered glucose metabolism. Intermittent hypoxemia and sleep fragmentation in sleep apnea can trigger a cascade of pathophysiological events, including autonomic activation, alterations in neuroendocrine function, and release of potent proinflammatory mediators such as tumor necrosis factor-alpha and interleukin-6. Epidemiologic and experimental evidence linking sleep apnea and disorders of glucose metabolism is reviewed and discussed here. Although the cause-and-effect relationship remains to be determined, the available data suggest that sleep apnea is independently associated with altered glucose metabolism and may predispose to the eventual development of Type 2 diabetes mellitus.
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PMID:Disorders of glucose metabolism in sleep apnea. 1622 61

The dietary effects of hyperglycemia increasingly result in type 2 diabetes in humans. Two species, the spiny mice (Acomys cahirinus) and the desert gerbil (Psammomys obesus), which have different metabolic responses to such effects, are discussed. Spiny mice exemplify a pathway that leads to diabetes without marked insulin resistance due to low supply of insulin on abundant nutrition, possibly characteristic of a desert animal. They respond with obesity and glucose intolerance, beta-cell hyperplasia, and hypertrophy on a standard rodent diet supplemented with fat-rich seeds. The accompanying hyperglycemia and hyperinsulinemia are mild and intermittent but after a few months, the enlarged pancreatic islets suddenly collapse, resulting in loss of insulin and ketosis. Glucose and other secretagogues produce only limited insulin release in vivo and in vitro, pointing to the inherent disability of the beta-cells to respond with proper insulin secretion despite their ample insulin content. On a 50% sucrose diet there is marked lipogenesis with hyperlipidemia without obesity or diabetes, although beta-cell hypertrophy is evident. P.obesus is characterized by muscle insulin resistance and the inability of insulin to activate the insulin signaling on a high-energy (HE) diet. Insulin resistance imposes a vicious cycle of Hyperglycemia and compensatory hyperinsulinemia, leading to beta-cell failure and increased secretion of proinsulin. Ultrastructural studies reveal gradual disappearance of beta-cell glucokinase, GLUT 2 transporter, and insulin, followed by apoptosis of beta-cells. Studies using the non-insulin-resistant HE diet-fed animals maintained as a control group are discussed. The insulin resistance that is evident to date in the normoglycemic state on a low-energy diet indicates sparing of glucose fuel in muscles of a desert-adapted animal for the benefit of glucose obligatory tissues. Also discussed are the effect of Psammomys age on the disabetogenicity of the HE diet; the impaired function of several components of the insulin signal transduction pathway in muscles, which reduces the availability of GLUT4 transporter; the testing of several antidiabetic modalities for the prevention of nutritional diabetes in Psammomys; and various complications related to the diabetic condition.
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PMID:Nutritionally induced diabetes in desert rodents as models of type 2 diabetes: Acomys cahirinus (spiny mice) and Psammomys obesus (desert gerbil). 1680 96

A 32-year-old man with a family history of type 2 diabetes mellitus presented with circulatory collapse and deep coma after 9 days of treatment with perospirone hydrochloride, a recently developed atypical antipsychotic agent available only in Japan. The new drug had been added to the long-standing treatment with risperidone. Diagnosed with diabetic ketoacidosis, he was given insulin and saline with discontinuation of all antipsychotics. Ultimately, diabetes was controlled by dietary therapy alone despite reintroduction of risperidone. The risk of new-onset diabetic ketoacidosis in patients with diabetic risk factors who are taking perospirone hydrochloride or other atypical antipsychotics should be kept in mind.
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PMID:New-onset diabetic ketoacidosis induced by the addition of perospirone hydrochloride in a patient treated with risperidone. 1730 17

Type 2, non-insulin-dependent diabetes has been increasing exponentially over the past decade and a half and it is estimated that within short it will comprise more than 350 million patients. The pathophysiology of type 2 diabetes is complex, but has two dominating factors, insulin resistance (which is mainly due to obesity and physical inactivity), and deficient insulin production. Indeed, although approximately 80% of type 2 diabetics are obese, 2/3 of overweight or obese persons show normal glucose metabolism. Data accumulated over the past few decades unequivocally indicate that diabetes can not develop in the absence of a major deficiency of insulin secretion. This deficiency is characterised by an early loss of first-phase insulin response to glucose, followed by gradual collapse of the later insulin response as well as of the maximal secretory capacity of the beta-cell. Interestingly, functional modifications in the beta-cell do not present a discontinuity; in fact, some of the characteristics of the diabetic beta-cell function can be found in a fraction of the healthy population. A major challenge has been to answer the question whether the population with decreased insulin secretory capacity represents the substratum from which future diabetics emerge. While many observations suggest that such may indeed be the case, conclusive evidence is still unavailable. The search for the beta-cell molecular mechanisms which prepare the ground for diabetes has been difficult and mainly limited to laboratory models of type 2 diabetes. Greater success has been achieved in elucidating the secondary beta-cell defects elicited once diabetes is established and the beta-cell exposed to chronically elevated glucose and fatty acid levels (so-called gluco-lipotoxicity). The latter reduces the responsiveness of insulin secretion to physiological stimuli, as it impairs the biosynthesis and processing of proinsulin. The leptin resistance of obesity certainly plays a role in this context, since leptin reduces, i.a., the lipid content of the islet. Similarly, the reduced adiponectin levels of obesity favour diminished beta-cell function. Nevertheless, it seems probable that the most important negative factor for the beta-cell in obesity is the inflammatory state. Indeed, several cytokines are deleterious for the beta-cell and may play a role in the pathogenesis of the islet dysfunction of diabetes, as demonstrated by the recent work of Donath and coworkers. We propose the working hypothesis that the "prediabetic" beta-cell in fact is a normal beta-cell whose functional capabilities (insulin secretion and biosynthesis, cell proliferation, resistance to stress...) is at the lower-end of the normal distribution. At times of "reasonable" metabolic requirements, i.e. reasonable energy balance, such a "prediabetic" beta-cell is fully adequate to cover the insulin needs of the organism. Insulin production by the "prediabetic" beta-cell becomes insufficient either when insulin needs become excessive, as is the case in over-nutrition (with or without insulin resistance), or when beta-cell function and adaptation are impaired by "external" factors such as the obesity-related inflammatory cytokines. Thus, deficient beta-cell function is seen as a relative factor against the metabolic background dictated by environmental factors. Type 2 diabetes is a hereditary disease, and many genes have been shown to be linked to diabetes. Our hypothesis is that such genes (or rather their polymorphism) define the range of the functional adaptability of the beta-cell to metabolic demand. This would be an excellent example of gene-environment interaction. Thus, we do not believe that sensu stricto diabetes genes exist. Against the above, optimal diabetes treatment would necessitate--reduction of the metabolic demand on the beta-cell,--support of its function and adaptive capabilities. Several new research avenues, discussed in the present meeting, may open new and improved therapeutic approaches for type 2 diabetes.
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PMID:[And what about diabetes?]. 1822 48

Obstructive Sleep Apnoea Syndrome (OSAS) is a common disorder, characterised by repetitive episodes of partial or complete obstruction of the upper airway during sleep and associated with increasing respiratory efforts. These perturbations lead, in turn, to oxyhaemoglobin desaturation, sleep fragmentation, and daytime symptoms, mainly excessive sleepiness. Accumulating evidence suggests that intermittent hypoxia and oxyhaemoglobin desaturation may result, independently of obesity, in impaired glucose metabolism, as well as insulin resistance even in non-diabetic patients with OSAS. Additionally, OSAS has been proposed as an independent risk factor for type 2 diabetes mellitus. Continuous Positive Airway Pressure (CPAP) is the treatment of choice for OSAS, since it eliminates upper airway collapse during sleep and also improves sleep fragmentation, daytime symptoms and quality of life. Moreover, it has been proposed that the amelioration of breathing disturbances during sleep can improve several markers of glucose metabolism and insulin resistance, such as glycated haemoglobin, fasting glucose, insulin, and insulin resistance. Indeed, some studies have reported improvements in these parameters especially in compliant patients. However, other works failed to confirm this beneficial effect. The present article reviews the issue whether CPAP treatment exerts a beneficial effect on glucose metabolism and insulin resistance.
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PMID:Continuous positive airway pressure treatment in patients with sleep apnoea: does it really improve glucose metabolism? 2038 Jun 27

Extreme hyperkalaemia is a life-threatening electrolyte disorder. It is relatively common in patients with severe renal insufficiency. This report describes a case of extreme hyperkalaemia caused by drugs in an 82-year-old female patient without severe renal insufficiency, who was successfully treated without haemodialysis. The patient had been treated for arterial hypertension and type 2 diabetes mellitus for 30 years. Over the last years she had been receiving enalapril and metformin. Three weeks before the admission to the hospital, she was receiving a non-steroidal anti-inflammatory drug (NSAID) because of the back pain. She was admitted to hospital due to a collapse and weakness in the limbs. Laboratory tests showed extreme hyperkalaemia, high blood sugar, metabolic acidosis, elevated serum creatinine and blood urea nitrogen (BUN), and a slightly elevated serum sodium. On ECG, we noticed typical signs of hyperkalaemia.The patient was treated with a slow intravenous bolus of calcium gluconate and intravenous infusion of sodium chloride with insulin, glucose with insulin and sodium bicarbonte. After the treatment, all laboratory findings normalised together and the patient felt better. This case shows that physicians should be very careful when prescribing NSAIDs to elderly patients treated with drugs that affect renal function.
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PMID:Extreme hyperkalaemia caused by concomitant use of a NSAID and an ace inhibitor in an elderly patient. 2058 99

Adiponectin, a hormone secreted from adipocytes, has been shown to protect against development of insulin resistance, ischemia-reperfusion injury, and inflammation. Adiponectin assembles into multiple oligomeric isoforms: trimers, hexamers and several higher molecular weight (HMW) species. Of these, the HMW species are selectively decreased during the onset of type 2 diabetes. Despite the critical role of HMW adiponectin in insulin responsiveness, its assembly process is poorly understood. In this report, we investigated the role of divalent cations in adiponectin assembly. Purified adiponectin 18mers, the largest HMW species, did not collapse to smaller oligomers after treatment with high concentrations of EDTA. However, treatment with EDTA or another chelator DTPA inhibited the oligomerization of 18mers from trimers in vitro. Zn(2+) specifically increased the formation of 18mers when compared with Cu(2+), Mg(2+), and Ca(2+). Distribution of adiponectin oligomers secreted from zinc chelator TPEN-treated rat adipocytes skewed toward increased proportions of hexamers and trimers. While we observed presence of zinc in adiponectin purified from calf serum, the role of zinc in disulfide bonding between oligomers was examined because the process is critical for 18mer assembly. Surprisingly, Zn(2+) inhibited disulfide bond formation early in the oligomerization process. We hypothesize that initial decreases in disulfide formation rates could allow adiponectin subunits to associate before becoming locked in fully oxidized conformations incapable of further oligomerization. These data demonstrate that zinc stimulates oligomerization of HMW adiponectin and possibly other disulfide-dependent protein assembly processes.
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PMID:Zinc enhances adiponectin oligomerization to octadecamers but decreases the rate of disulfide bond formation. 2223 97


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