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

The potency of highly active antiretroviral therapy, including protease inhibitors have led to declining morbidity and mortality in patients with HIV infection. However the use of protease inhibitors is associated with onset of morphologic and metabolic disorders. A syndrome of lipodystrophy has been described. It is characterized by fast wasting of the face and limbs, and a central adiposity, breast hypertrophy and buffalo neck. The prevalence of lipodystrophy in patients treated with protease inhibition is about 60%. The principal metabolic disorders are lipid abnormalities, principally hypertriglyceridemia. New onset of diabetes mellitus is less frequent. The pathogenesis of these abnormalities unknown. Insulin resistance seems to be a common feature of protease inhibitor associated metabolic an morphologic side-effects.
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PMID:[Metabolic complications associated with use of protease inhibitors]. 1092 55

Insulin-like growth factor (IGF) binding protein-1 (IGFBP-1) is a 28-kDa plasma protein that binds to IGF-I and IGF-II with high affinity. IGFBP-1 is elevated in the blood as a result of sepsis, AIDS, excessive alcohol consumption, and diabetes and may, in part, be responsible for the wasting observed during these pathophysiological conditions. The liver is the principal site of IGFBP-1 synthesis, and we have previously shown that proinflammatory cytokines can directly stimulate IGFBP-1 secretion in a human hepatoma cell line (HepG2). The purpose of the present study was to investigate the role of the MAP kinase pathway in regulating IGFBP-1 synthesis by IL-1beta. We show that IL-1beta stimulates the phosphorylation of ERK-1 and -2 in a time- and dose-dependent manner. In addition, the MAP kinase-kinase MEK-1 and the ribosomal S6-kinase RSK-1 are also phosphorylated in response to IL-1beta. The transcription factor CREB, a potential substrate of both protein kinase A (PKA) and RSK-1, is phosphorylated in response to IL-1beta and cAMP in HepG2 cells. The ability of IL-1beta to stimulate the expression of IGFBP-1 and the phosphorylation of the above kinases was specifically inhibited by PD98059, a MEK-1 inhibitor. cAMP also stimulated IGFBP-1 synthesis, but PD98059 failed to block the cAMP effect. Conversely, a PKA inhibitor (H-89) inhibited the ability of cAMP, but not IL-1beta to stimulate IGFBP-1 synthesis. The effect of IL-1beta and cAMP on IGFBP-1 messenger RNA (mRNA) accumulation was additive. IL-1beta, cAMP, PD98059, and H-89 had similar effects on the accumulation of IGFBP-1 protein and mRNA. IL-1beta and cAMP did not change the half-life of IGFBP-1 mRNA, but PD98059 and SB202190, a p38 MAP kinase inhibitor, destabilized IGFBP-1 mRNA and blocked the phosphorylation of RSK-1 in response to IL-1beta. Our data demonstrate that the MAP kinase signal transduction pathway plays an important role in the regulation of IGFBP-1 synthesis by IL-1beta.
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PMID:Stimulation of insulin-like growth factor binding protein-1 synthesis by interleukin-1beta: requirement of the mitogen-activated protein kinase pathway. 1096 86

Studies which evaluate the psychosocial development and integration of adult female congenital adrenal hyperplasia (CAH) patients are rare but show that patients with the salt wasting form are significantly more virilized and more frequently single and childless. Major complaints are irregular menstruation, hirsutism, acne, obesity, deep voice, and cushingoid features. Surprisingly, a higher prevalence of psychosomatic disorders has not yet been described. Since anorexia nervosa (AN) has not yet been described in patients with CAH, we here report 4 cases of female CAH patients who developed AN during adolescence. Diagnosis of CAH was made between the age of 10 days and 3 years. Three patients suffer from the simple-virilizing form of CAH, one patient has a mild salt wasting CAH. Genital malformation varied from Prader stage II to IV. All 4 patients were compound heterozygotes for mutations/deletions of the CYP21B gene. Control of substitution therapy consisting of hydrocortisone and fluorocortisone was good. AN developed at ages 12, 13, 17, and 21 years (ICD 10 criteria for AN are BMI below 17.5 kg/m2, deliberate weight loss, body image disturbance, and primary or secondary amenorrhoea). Diagnosis of AN was established by psychiatrists and/or psychologists. All four patients showed an impressive and deliberate weight loss between 13 and 20 kg within 6 months, had primary or secondary amenorrhoea, and presented with BMI between 13 and 17.9 kg/m2. All patients received psychological treatment and recovered. However, one patient had a severe relapse of AN. Two patients are now married and one has a healthy son. These cases demonstrate that the diagnosis of CAH is compatible with the development of AN and illustrate the importance of providing treatment for CAH patients that encompasses not only medical but also psychological and social care.
Exp Clin Endocrinol Diabetes 2000
PMID:Anorexia nervosa in congenital adrenal hyperplasia: long-term follow-up of 4 cases. 1102 57

The ubiquitin-proteasome system is thought to play a major role in normal muscle protein turnover and to contribute to diabetes-induced protein wasting in skeletal muscle. However, its importance in cardiac muscle is not clear. We measured heart muscle mRNA for ubiquitin and for the C2 and C8 proteasomal subunits, the amount of free ubiquitin and the proteasome chymotrypsin-like proteolytic activity in control and diabetic rats. Results were compared to those in skeletal muscle (rectus). Heart ubiquitin, C2 and C8 subunit mRNA and proteolytic activity were significantly greater than in skeletal muscle (P </= 0.05). This suggests that the ubiquitin proteasomal pathway may also be important for normal heart muscle turnover. Diabetes increased ubiquitin mRNA by approximately 50% in heart (P < 0.03) and by approximately 100% in skeletal muscle (P < 0.005). It remained high after 3 days of insulin treatment in both tissues. C2 and C8 subunit mRNA did not change with diabetes or insulin treatment. Diabetes did not change the amount of free ubiquitin or the proteasomal (lactacystin-inhibitable) chymotrypsin-like peptidase activity in heart or skeletal muscle. In conclusions, gene expression for several components of the ubiquitin-proteasome proteolytic pathway is significantly higher in cardiac than in skeletal muscle, as is the proteasome chymotrypsin-like peptidase activity. Diabetes increases the expression of ubiquitin but not C2 or C8 subunit mRNA, nor does it significantly alter the amount of free ubiquitin or the proteasome chymotrypsin-like peptidase activity. The rate-limiting step of enhanced protein degradation in diabetic rat heart and skeletal muscle may be located at ubiquitin conjugation and/or its binding to proteasome, not at the ubiquitin availability or the proteasome itself.
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PMID:The ubiquitin-proteasome proteolytic pathway in heart vs skeletal muscle: effects of acute diabetes. 1102 19

In an effort to characterize the basis of abnormalities in body weight regulation (i.e. wasting) in Huntington's disease (HD), we examined adipocytes in a transgenic model of HD, the R6/2 mouse. These mice typically show severe wasting beginning at approximately 12 weeks of age and die between 12 and 15 weeks. Despite an overall growth retardation compared with wild-type littermates, we observed an enhanced accumulation of body fat at 8-9 weeks of age in R6/2 mice fed laboratory chow or a synthetic high fat, high sugar diet. The obesity was not accompanied by symptoms associated with diabetes, as there were no abnormalities in serum glucose, serum insulin or the ability of insulin to stimulate glucose metabolism in epididymal adipose tissue. As expected, the obesity in the high fat, high sugar-fed R6/2 mice was accompanied by increased serum leptin. The ability of insulin to stimulate leptin release from isolated epididymal adipose tissue was also enhanced in R6/2 mice. In contrast, the ability of isoproterenol to inhibit leptin release was reduced in adipose tissue from R6/2 mice, as was the lipolytic effect of isoproterenol. These data suggest that the obesity observed at 8-9 weeks in R6/2 mice may stem from a defect in fat breakdown by adipocytes.
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PMID:Abnormalities in the functioning of adipocytes from R6/2 mice that are transgenic for the Huntington's disease mutation. 1115 62

HIV patients taking protease inhibitors are sometimes reporting a wasting-related syndrome called lipodystrophy, Lipodystrophy is a condition in which the body does not process fats properly. Symptoms include loss of fat from the face and upper body, muscle loss in the arms and legs, pot belly, and abnormal fatty deposits referred to as buffalo humps. Diabetes occasionally occurs, and blood triglycerides are elevated. The syndrome was initially seen in patients on Crixivan, although use of other protease inhibitors can also cause this side effect. The forum for Collaborative AIDS Research is developing a clinical trial to learn more about this symptom. Patients experiencing the symptoms of lipodystrophy should contact the forum for Collaborative AIDS Research.
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PMID:Metabolic problems and PIs. 1136 32

Patients taking protease inhibitors are beginning to report a number of strange side effects that may be associated with the drugs, although that has not been conclusively proven. Side effects include new or exacerbated cases of diabetes or hyperglycemia, hemolytic anemia, spontaneous bleeding in hemophiliac patients, and changes in body composition. The first unusual symptoms were fatty deposits in the abdomen (Crix belly) and back (Buffalo humps), with wasting symptoms in the upper body. No hard data indicates that these symptoms are directly connected to protease inhibitor use. About 70 percent of all patients on protease inhibitors take Crixivan (indinavir). An Internet discussion group for patients to compare experiences with the drug is available.
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PMID:Protease inhibitor side effects take people by surprise. 1136 85

Of all the risk factors to cardiovascular disease (CVD), age is the most powerful: CVD incidence and prevalence rise progressively at all ages beyond young adulthood. This reflects the central role of time, and hence duration, in the atherogenic process. It also reflects age-related changes in physiology - notably alterations in body mass and composition favoring increased adiposity and in sex hormone secretion (combining adverse effects of androgens on lipoprotein lipid levels in males, lowering HDL, and of the decline in estrogens in postmenopausal females, raising LDL). The interactions among the passage of time, these physiological changes and perhaps aging per se, and pathological forces such as cigarette smoking, hypertension, and genetically determined dyslipoproteinemia conspire to accelerate the rate of atherogenesis. Thus clinical atherosclerosis and its complications rise exponentially with increasing age in the population at large. However, the relationship between dyslipoproteinemia and CVD risk in the individual patient actually declines with advancing age. This apparent paradox reflects confounding introduced by the advent of disease processes that cause wasting and inflammation such as cancer, infection, diabetes, trauma, and even CVD that actually lower lipid levels, frequently to the level of hypocholesterolemia. Thus, while with age the population-attributable risk of hypercholesterolemia (and/or low HDL) rises, the cholesterol-attributable risk in the individual falls. As a result the prescription of lipid-lowering therapy in elderly patients requires exquisite individualization: patients most likely to benefit are those with existing CVD (i.e., in secondary prevention) who nevertheless enjoy robust health and are highly motivated to comply with demanding regimens of diet and exercise plus drugs where needed to reach target LDL levels (less than 100 mg/dl). At the other extreme are those least likely to benefit: patients who are frail and failing from CVD or other wasting diseases of old age that present a more immediate threat to survival.
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PMID:Aging and Atherosclerosis: Changing Considerations in Cardiovascular Disease Prevention as the Barrier to Immortality is Approached in Old Age. 1141 41

A 48-year-old man with a 14-year history of type 2 diabetes with proliferative diabetic retinopathy and distal symmetrical diabetic polyneuropathy visited our hospital. Eight months later, he subacutely developed difficulty in both shoulder movement and trouble standing up from a squatting position. This was accompanied by severe bilateral shoulder and thigh pain. Magnetic resonance imaging of the brain, cervical and lumbar spine, computed tomography of the shoulder and X-ray films of the cervical spine and shoulder revealed no abnormality. Cerebrospinal fluid showed a mild elevation of protein (0.93 g/l) without cell infiltration. Antiganglioside antibodies and point mutation of mitochondrial DNA at position 3243 were not found. Neuropathology of the sural nerve showed a moderate myelinated fiber loss, active axonal degeneration, but onion-bulb formation, endoneurial or epineurial vasculitis were not observed. Electromyography revealed neurogenic changes in the proximal upper limb muscles. Nerve conduction studies revealed mild bilateral slowing in nerve conduction velocity in both of the upper and lower limbs. The diagnosis of this patients was suspected to be a proximal diabetic neuropathy (diabetic amyotrophy). The pain and muscle weakness had persisted more severely in the shoulder than in the thigh throughout the clinical course. His unbearable symptoms could be partially alleviated by an administration of a selective serotonin reuptake inhibitor, fluvoxamine maleate. Proximal diabetic neuropathy is a rare disabling type of neuropathy, which is characterized with subacute bilateral muscle weakness and wasting in the proximal part of the lower limbs. The involvement of the scapulohumeral region observed in this case is very unusual in proximal diabetic neuropathy.
Diabetes Res Clin Pract 2001 Oct
PMID:A suspected case of proximal diabetic neuropathy predominantly presenting with scapulohumeral muscle weakness and deep aching pain. 1153 31

Umbilical artery catheters are an essential aid in the treatment of newborn infants who have cardiopulmonary disease. However, it is well-known that umbilical artery catheterization is associated with complications. The most frequent visible problem in an umbilical line is blanching or cyanosis of part or all of a distal extremity or the buttock area resulting from either vasospasm or a thrombotic or embolic incidence. Ischemic necrosis of the gluteal region is a rare complication of umbilical artery catheterization. We report the case of a full-term infant of an insulin-dependent diabetic mother with poor blood glucose control who developed a left peroneal nerve palsy after ischemic necrosis of the gluteal region after umbilical artery catheterization. The infant was born weighing 5050 g. The mother of the infant had preexisting diabetes mellitus that was treated with insulin from the age of 14 years. The metabolic control of the mother had been unstable both before and during the pregnancy. The neonate developed respiratory distress syndrome soon after birth and was immediately transferred to the neonatal intensive care unit. Mechanical ventilation via endotracheal tube was quickly considered necessary after rapid pulmonary deterioration. Her blood glucose levels were 13 mg/dL. A 3.5-gauge umbilical catheter was inserted into the left umbilical artery for blood sampling without difficulty when the infant required 100% oxygen to maintain satisfactory arterial oxygen pressure. Femoral pulses and circulation in the lower limbs were normal immediately before and after catheterization. A radiograph, which was taken immediately, showed the tip of the catheter to be at a level between the fourth and fifth sacral vertebrae. The catheter was removed immediately. Circulation and femoral pulses were normal and no blanching of the skin was observed. Another catheter was repositioned and the tip was confirmed radiologically to be in the thoracic aorta between the sixth and seventh thoracic vertebrae. The catheter was continuously flushed with heparinized solution. Three days after umbilical arterial catheterization, bruising was observed over the left gluteal region. The catheter was immediately removed despite its correct position. Over the next few days, the bruised skin and underlying tissues became necrotic. The area affected was 3 x 4 cm in diameter, with central necrosis surrounded by a rim of dark, red skin, which, in turn, was sharply demarcated from normal skin by a narrow, pale zone. Surgical excision of the gluteal necrosis was performed, but a deep ulcer 3 cm in diameter was left. The gluteal ulcer required 1 month to heal completely with extensive scar tissue formation. Throughout this period, the infant showed active movements in all of her limbs. At 4 weeks of age deterioration of all movement below the left knee with a dropping foot was observed. Severe peroneal nerve palsy was confirmed through nerve conduction studies, and there was electromyographic evidence of degeneration of the muscles supplied by the peroneal branch of the sciatic nerve. A Doppler study, which was also conducted, revealed no vascular damage. Treatment with physiotherapy and night-splinting of the left ankle was instituted. Repeated examination and nerve conduction tests at 3 months showed slow improvement with the left peroneal nerve remaining nonexcitable. At the time of this writing, the infant is 6 months old, and muscular strength below the left knee is still weak and atrophic changes in the form of muscle-wasting are already present. The rest of her motor development is normal. In our case, gangrene of the buttocks and sciatic nerve palsy followed displacement of the tip of the catheter into the inferior gluteal artery, a main branch of the internal iliac artery supplying the gluteus maximus, the overlying skin, and the sciatic nerve. The gangrenous changes were probably caused by vascular occlusion resulting from catheter-induced vasospasm of the inferior gluteal artery. Sciatic nerve palsy associated with umbilical artery catheterization has been postulated to be caused by vascular occlusion of the inferior gluteal artery. Infants of diabetic mothers may exhibit changes in coagulation factors and be at increased risk of thrombotic complications in utero and postnatally. In addition, maternal diabetes mellitus is associated with an increased incidence of congenital abnormalities, the incidence of which is 3 to 5 times higher than that among nondiabetic mothers. Although no particular or specific abnormalities have been associated with maternal disabilities, abnormalities of the cardiovascular system, including the development of umbilical vessels, frequently occur. This complication of umbilical artery catheterization has not been widely reported. We describe the first case that refers to gluteal gangrene and peroneal nerve palsy after umbilical artery catheterization of a newborn infant of a diabetic mother with poor blood glucose control. It should be noted that there were no contributing factors except that of the displacement of the catheter into the inferior gluteal artery. We speculate that the displacement of the tip of the catheter, with no difficulty in the present case, was associated with the maldevelopment of normal branching patterns of arteries after exposure of the fetus to hyperglycemia. In conclusion, umbilical artery catheterization is possibly associated with vascular occlusion, particularly in infants of diabetic mothers. Frequent inspection after the procedure has been performed is of the utmost importance especially in these neonates who often suffer from cardiopulmonary disease and require catheterization of their umbilical artery.
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PMID:Peroneal nerve palsy: a complication of umbilical artery catheterization in the full-term newborn of a mother with diabetes. 1192 39


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