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)

We tested the hypothesis that pioglitazone could restore expression of heat shock protein (HSP)72 in insulin-resistant rat heart. At 12 weeks of age, male Otsuka Long-Evans Tokushima Fatty (OLETF) rats and control (LETO) rats were treated with pioglitazone (10 mg x kg(-1) x day(-1)) or glibenclamide (5 mg x kg(-1) x day(-1)) for 4 weeks. Thereafter, hyperthermia (43 degrees C for 20 min) was applied. In response to hyperthermia, the activation of serine/threonine kinase Akt depending on phosphatidylinositol 3 (PI3) kinase was necessary for cardiac expression of HSP72. Hyperthermia-induced activation of Akt and HSP72 expression were depressed in OLETF rat hearts. Pioglitazone but not glibenclamide improved insulin sensitivity in OLETF rats, which was associated with the restoration of Akt activation and HSP72 expression. In experiments with isolated perfused heart, reperfusion-induced cardiac functional recovery was suppressed in OLETF rat hearts, which was improved by pioglitazone but not glibenclamide. Our results suggest that PI3 kinase-dependent Akt activation, an essential signal for HSP72 expression, is depressed in the heart in insulin-resistant OLETF rats, and the results suggest also that the restoration of HSP72 expression and tolerance against ischemia/reperfusion injury by treatment with pioglitazone might be due to an improvement of insulin resistance, leading to restoration of impaired PI3 kinase-dependent Akt activation in response to hyperthermia.
Diabetes 2006 Aug
PMID:Pioglitazone but not glibenclamide improves cardiac expression of heat shock protein 72 and tolerance against ischemia/reperfusion injury in the heredity insulin-resistant rat. 1687 3

Although previous studies have shown increased risk of morbidity and mortality in patients with diabetes mellitus (DM) who undergo coronary artery bypass grafting (CABG), data are conflicting on whether the gains in physical function and mental health after CABG achieved by patients with DM are similar to, or less than, those achieved by patients without DM. We compared the gains in physical function and mental health at 6 months after CABG surgery between 696 consecutive patients with DM and 376 without DM who underwent their first CABG from February 1999 to February 2001. Physical function and mental health were measured using the Short Form 36-item Health Survey. From the baseline and follow-up Short Form 36-item Health Survey data, the physical and mental component scales were derived. At 6 months, the patients with and without DM had significant improvement in physical function and mental health, but those without DM had improved significantly more than those with DM with respect to physical functioning. After adjusting for baseline characteristics, a lower proportion of patients with DM had experienced improvement (an increase of > or = 5 points) in the physical component scale score compared with those without DM (45.0% vs 58.0.%, RR = 0.78, p = 0.002). Moreover, a higher proportion of patients with DM experienced a decrease in the physical component scale score compared with those without DM (14.9% vs 7.8%, RR = 1.91, p = 0.006). In contrast, no significant differences were found in the mental component scale score changes by DM status. In conclusion, CABG is associated with lower gains in physical function in those with DM than in those without DM. Special attention should be paid to the physical function of patients with DM after CABG, and any barriers to functional recovery in this group should be promptly identified and addressed.
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PMID:Comparison of functional status after coronary artery bypass grafting in patients with and without diabetes mellitus. 1692 48

The use of cardiac magnetic resonance (CMR) has emerged in the last decades. Technical innovations provide fast and high-quality imaging sequences and CMR is often proposed as a gold-standard for the in vivo evaluation of cardiac function, morphologic details and infarct size. Also the 31-phosphorous magnetic resonance spectroscopy (MRS) is a unique tool to investigate the human myocardial high-energy phosphate (HEP) metabolism in vivo. PCr/b-ATP ratio examined by MRS is mainly used as an index for cardiac energy metabolism. We have described decreased PCr/b-ATP ratios in patients with diabetes mellitus, hypercholesterolemia and hemochromatosis. The use of CMR to study the effects of ischemia time on the evolution of myocardial infarct characteristics after an acute myocardial infarction (AMI) treated with a primary angioplasty (p-PTCA) is a promising new application of this technique. Results of this study will further help to clarify the impact of ischemia time on myocardial regional functional recovery after p-PTCA.
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PMID:[Magnetic resonance tomography and spectroscopy investigations of the human heart]. 1734 62

This study was done to test the hypothesis that simulated vaginal birth by vaginal distension (VD) causes more severe urinary incontinence and slower recovery in diabetic rats. After measuring baseline leak point pressure (LPP) in 16 diabetes mellitus (DM) and 16 age- and weight-matched control (Ct) female Sprague-Dawley rats, these animals underwent either VD or sham VD (sham). Four and ten days after the procedures, LPP and conscious cystometry were assessed. Tissues were then harvested and examined by light microscopy. LPP at baseline was equal among all four groups. Four days after VD, LPP in both VD groups dropped to significantly lower levels than in sham rats (P < 0.001). Moreover, LPP in the DM+VD group was significantly lower than in the Ct+VD group. At 10 days, LPP in the Ct+VD group had recovered to its baseline value, whereas the LPP in the DM+VD group remained significantly reduced. DM rats had larger bladder capacity and longer voiding intervals than Ct rats. Histological findings included more severe damage to the external sphincter striated musculature of the urethra in DM+VD group compared with Ct+VD. In conclusion, these findings suggest that DM causes increased severity and delayed functional recovery from the effects of simulated childbirth.
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PMID:Diabetes slows the recovery from urinary incontinence due to simulated childbirth in female rats. 1749 Nov 7

Adrenalectomy continues to play an important role in the management of Cushing's syndrome (CS). Untreated CS causes considerable physical and mental morbidity and mortality. However, little information is available on the effect of adrenalectomy in ameliorating functional disabilities in CS patients. Our study assesses the long-term outcome of adrenalectomy in patients with CS. This is a retrospective analysis of CS patients managed during 1990-2005 at a tertiary care center. We analyzed the clinical presentation, endocrine evaluation, and surgical management preoperatively and following adrenalectomy. The subjects were 37 patients with CS (age 24.5 +/- 15 years, range 1-60 years; male:female 1.0:1.2). There were various etiologies--unilateral adrenocortical adenoma (n = 11), adrenocortical carcinoma (n = 13), pituitary ACTH-secreting adenoma with failed transsphenoidal surgery (n = 4), ectopic unidentified ACTH source (n = 7), bilateral adrenal macronodular hyperplasia (n = 1), primary pigmented nodular adrenal hyperplasia (n = 1) --for which the patients underwent adrenalectomy: unilateral (n = 22), bilateral (n = 13), or adrenonephrectomy (n = 2). Two patients died during the perioperative period owing to chest infection and sepsis. At the median follow-up of 60 months (range 6-144 months), the patients exhibit significant persistence of obesity (41%), proximal muscle weakness (44%), menstrual irregularity (8%), hypertension (31%), and insulin-dependent diabetes (29%). Hirsutism and psychological abnormalities persisted to a lesser extent. All patients had biochemical cure of CS following surgery evidenced by the 8 a.m. basal cortisol < or = 5 microg/dl. The hypothalamic-pituitary-adrenal axis recovered as shown by normalization of the short synacthen-stimulated cortisol level (peak level > or = 20 microg/dl) after a median follow-up of 9 months (range 6-18 months). Incomplete clinical recovery following adrenalectomy emphasizes the need of early recognition and prompt treatment of CS. Surgery for adrenocortical adenoma is safe and effective; however, survival of patients with CS due to adrenocortical carcinoma remains poor. Bilateral adrenalectomy provides early control of hypercortisolism in selected cases of unlocalized ectopic ACTH syndrome or failed transsphenoidal surgery. Even though functional recovery is incomplete after adrenalectomy, quality of life improves considerably.
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PMID:Outcome of adrenalectomy for Cushing's syndrome: experience from a tertiary care center. 1753 56

In diabetes-related amputations, the risk of nonhealing or infection of a wound and the need for revision are increased. Medical treatment before amputation should optimize general and local conditions including the regression of edema, the control of infection, and the optimization of glucoregulation. A major argument for foot-sparing surgery is the poor functional recovery after major limb amputation. Diabetic patients are frail, with an increased postoperative morbidity and mortality after major amputation. Factors detrimental to functional outcome are advanced age, end-stage renal disease, dementia, and above-knee amputation. A multidisciplinary approach is required to optimize the results of diabetes-related amputations. The authors discuss medical and technical aspects that may reduce the failure of minor or major diabetes-related amputations.
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PMID:Amputation in diabetic patients. 1761 92

The Copenhagen Stroke (COST) Study was a prospective, consecutive, community-based study of 1,197 patients with acute stroke who underwent acute stroke care and rehabilitation in a stroke unit setting. This article reviews the results of this study with respect to (1) the effect of organized stroke care and rehabilitation, (2) neurological outcome and functional outcome of stroke in relation to initial stroke severity and functional disability, (3) recovery of upper-extremity function and walking, (4) time course of neurological and functional recovery relative to initial stroke severity, (5) mechanisms of stroke recovery, and (6) the effect on stroke recovery of various demographic, medical, and pathophysiological factors, such as stroke in progression, spontaneous reperfusion age, diabetes, blood glucose on admission, stroke type (hemorrhage/infarction), silent infarction, and leuco-araiosis.
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PMID:The Copenhagen Stroke Study experience. 1789 59

Chronic spinal cord injury (SCI) is associated with the development of serious medical concerns. In fact, it is increasingly well documented that most SCI patients who survive the first 24 hr will rapidly develop, within a few months to a few years, cardiovascular problems, type II diabetes, muscle wasting, osteoporosis, immune deficiencies, and other life-threatening problems. The cellular mechanisms underlying these so-called secondary health complications remain unclear, and no drug or standard approach has been developed to specifically treat these complications. To investigate the cellular and metabolic changes associated with chronic SCI and functional recovery, work mainly from our laboratory recently has led to the characterization of a mouse model of chronic paraplegia. This review reports cellular, systemic, and metabolic changes (associated mainly with secondary health complications) occurring within a few days to a few weeks after SCI in low-thoracic spinal cord-transected mice. We also describe our research platform developed to ease technological transfer and to accelerate drug-screening studies in animals. A global understanding of the many chronic changes occurring after SCI together with efficient tools and approaches for testing new or existing drug candidates is likely to yield the design of innovative treatments against secondary complications that combine cellular plasticity-modulating agents, locomotor network-activating drugs, hormonal therapy, and exercise training.
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PMID:A technological platform to optimize combinatorial treatment design and discovery for chronic spinal cord injury. 1861 46

Demyelinating disease is pathologically characterized by the death of mature oligodendrocytes that normally synthesize myelin to perform insulating functions. Moreover, demyelinating disease also results in the failure of remyelination process in which oligodendrocyte progenitor cells reactivate and differentiate into new oligodendrocytes. Thus, this disease reflects decreased nerve conduction velocity and eventually dysfunction of the nervous system. A notable fact in the clinic is that demyelination is one of the most common diabetes-induced complications, implying that demyelinating disease may be relevant to insulin deficiency in vivo. However, the explicit pathological relationship between demyelination and diabetes remains unclear. Mainstream theories posit that demyelinating disease is an autoimmune disease arising from abnormal immunological reactions, but this perspective is limited when applied to the clinic. Olig1 is a vital transcription factor involved in oligodendrogenesis and is essential for the survival and maturation of oligodendrocyte progenitor cells. Furthermore, Olig1 is required for the onset of remyelination in adults. In the present study, we serendipitously found by means of protein immunoblot that the expression of nuclear Olig1 was inhibited when mouse oligodendrocyte progenitor cells were cultured in the absence of insulin. Combining this finding with the clinical relevance of demyelination and diabetes, we hypothesize that in vivo insulin deficiency impairs the reactivation and differentiation of oligodendrocyte progenitor cells through downregulation of nuclear Olig1 expression and therefore hinders the remyelination, which is an important process required for functional recovery in demyelinating disease. This hypothesis implies that in vivo insulin deficiency may be a novel etiological cause of demyelinating disease and thus contribute to improved the clinical therapies for remyelination repair. We suggest that sustaining normal insulin levels and stable nuclear Olig1 expression in vivo can be new therapeutic targets for remyelination repair and diabetic neuropathy. In addition, with respect to the clinical transplantation of oligodendrocyte progenitor cells for remyelination repair, supplementing cell suspensions that are to be transplanted with appropriate doses of insulin potentially may facilitate adaptation of the transplanted progenitor cells to the heterogeneous and pathological environment in vivo and eventually improve the efficacy of the cellular transplantation.
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PMID:Invivo insulin deficiency as a potential etiology for demyelinating disease. 1862 85

The present article presents correlations of frailty associated functional changes in older patients with the development and progression of cerebrovascular disease (CVD). Special focus is drawn on the impact of well established risk factors for the development of CVD such as diabetes, hypertension and smoking on frailty markers especially in the light of functional recovery following an acute cerebrovascular event.
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PMID:[Cerebrovascular disease]. 1867 94


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