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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetic rats both overeat high-carbohydrate diet and have altered hypothalamic neuropeptide Y (NPY) and corticotropin-releasing factor (CRF). In contrast, a high-fat diet reduces caloric intake of diabetics to normal, reflected by normal hypothalamic NPY and CRF content. How the brain senses these changes in diet is unknown. To date, no hormonal changes explain these diet-induced changes in caloric intake. We tested whether the common branch of the hepatic vagus mediates the fat signal. We presented fat in two ways. First, diabetic and vehicle-treated rats were offered a cup of lard in addition to their normal high-carbohydrate diet. Second, we switched diabetic rats from high-carbohydrate diet to high-fat diet, without choice. In streptozotocin-treated rats, both methods resulted in fat-induced inhibition of caloric intake and normalization of hypothalamic neuropeptides to nondiabetic levels. Strikingly, common branch hepatic vagotomy (unlike gastroduodenal vagotomy) entirely blocked these fat-induced changes. Although a shift in hepatic energy status did not explain the lard-induced changes in diabetic rats, the data suggested that common hepatic branch vagotomy does not interfere with hepatic energy status. Furthermore, common branch hepatic vagotomy without diabetes induced indexes of obesity. Abnormal function of the hepatic vagus, as occurs in diabetic neuropathy, may contribute to diabetic obesity.
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PMID:The hepatic vagus mediates fat-induced inhibition of diabetic hyperphagia. 1294 72

The results of the study of sleep apnea (SA) in different forms of neurological disorders (cerebral stroke, diabetic polyneuropathy, neuromuscular diseases and amyotrophic lateral sclerosis--ALS) are presented. Two hundred and two patients, 103 male and 99 female, aged 17-84 years, have been investigated, using questionnaires and polysomnography. Nocturnal recording of EEG, EMG, electrooculography, oronasal air flow, respiratory thorax and abdomen movements, oxyhemoglobin saturation and breathing sounds has been performed. Clinical features of sleep apnea (SA) were most prominent in patients with neuromuscular diseases (58%) and ALS (54%), however the nocturnal study confirmed the presence of SA in patients with diabetic polyneuropathy (53%, mean RDI 15.7 +/- 18.7 epis./h) and cerebral stroke (41%, mean RDI 12.6 +/- 15.6 epis./h). A comparison of the patient's characteristics and sleep breathing indices revealed that factors of neurological damage contribute most significantly to ALS, but in diabetic neuropathy, age and obesity play a greater role.
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PMID:[Sleep apnea in neurological disorders]. 1507 37

The molecular mechanism responsible for obesity-associated insulin resistance has been partially clarified: increased fatty acid levels in muscle fibers promote diacylglycerol synthesis, which activates certain isoforms of protein kinase C (PKC). This in turn triggers a kinase cascade which activates both IkappaB kinase-beta (IKK-beta) and c-Jun N-terminal kinase (JNK), each of which can phosphorylate a key serine residue in IRS-1, rendering it a poor substrate for the activated insulin receptor. Heat shock proteins Hsp27 and Hsp72 have the potential to prevent the activation of IKK-beta and JNK, respectively; this suggests that induction of heat shock proteins may blunt the adverse impact of fat overexposure on insulin function. Indeed, bimoclomol--a heat shock protein co-inducer being developed for treatment of diabetic neuropathy--and lipoic acid--suspected to be a heat shock protein inducer--have each demonstrated favorable effects on the insulin sensitivity of obese rodents, and parenteral lipoic acid is reported to improve the insulin sensitivity of type 2 diabetics. Moreover, there is reason to believe that heat shock protein induction may have a favorable impact on the microvascular complications of diabetes, and on the increased risk for macrovascular disease associated with diabetes and insulin resistance syndrome. Heat shock protein induction may also have potential for preventing or treating neurodegenerative disorders, controlling inflammation, and possibly even slowing the aging process. The possible complementarity of bimoclomol and lipoic acid for heat shock protein induction should be assessed, and further efforts to identify well-tolerated agents active in this regard are warranted.
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PMID:Induction of heat shock proteins may combat insulin resistance. 1630 49

Peripheral neuropathy is a common problem encountered by neurologists and primary care physicians. While there are many causes for peripheral neuropathy, none can be identified in a large percentage of patients ("idiopathic neuropathy"). Despite its high prevalence, idiopathic neuropathy is poorly studied and understood. There is evolving evidence that impaired glucose tolerance (prediabetes) is associated with idiopathic neuropathy. Preliminary data from a multicenter study of diet and exercise in prediabetes (the Impaired Glucose Tolerance Neuropathy Study) suggests a diet and exercise counseling regimen based on the Diabetes Prevention Program results in improved metabolic measures and small fiber function. Prediabetes is part of the Metabolic Syndrome, which also includes hypertension, hyperlipidemia and obesity. Individual aspects of the Metabolic Syndrome influence risk and progression of diabetic neuropathy and may play a causative role in neuropathy both for those with prediabetes, and those with otherwise idiopathic neuropathy. Thus, a multifactorial treatment approach to individual components of Metabolic Syndrome may slow prediabetic neuropathy progression or result in improvement.
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PMID:Idiopathic neuropathy, prediabetes and the metabolic syndrome. 1644 68

As a result of epidemiologic transition, diabetes mellitus became a major public health problem in Tunisia. We tried to determine the epidemiological and clinical features of patients with type 2 diabetes mellitus in primary health care units in Sousse (Tunisia). It was a cross sectional study about a stratified sample of 404 type 2 diabetes mellitus patients followed in primary care offices in Sousse in 2003. Average age was 60 + 10.9 years and sex-ratio was 0.5. Hypertension and obesity were found in respectively 71.3% and 37.6%. Diabetic neuropathy was the most frequent degenerative complication (41.1%) followed by diabetic retinopathy (18.3%). Thus, type 2 diabetes mellitus patients, followed in primary care units show a high cardiovascular risk with serious and frequent complications. That's why, the national care program of type diabetes mellitus, in primary health care should take in consideration, in its guidelines, the clinical and epidemiological characteristics of these patients.
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PMID:[Epidemiologic and clinical features of patients with type 2 diabetes mellitus in primary care facilities (Sousse, Tunisie)]. 1703 32

Whereas functional, metabolic, neurotrophic, and morphological abnormalities of peripheral diabetic neuropathy (PDN) have been extensively explored in streptozotocin-induced diabetic rats and mice (models of type 1 diabetes), insufficient information is available on manifestations and pathogenetic mechanisms of PDN in type 2 diabetic models. The latter could constitute a problem for clinical trial design because the vast majority of subjects with diabetes have type 2 (non-insulin dependent) diabetes. This study was aimed at characterization of PDN in leptin-deficient (ob/ob) mice, a model of type 2 diabetes with relatively mild hyperglycemia and obesity. ob/ob mice ( approximately 11 weeks old) clearly developed manifest sciatic motor nerve conduction velocity (MNCV) and hind-limb digital sensory nerve conduction velocity (SNCV) deficits, thermal hypoalgesia, tactile allodynia, and a remarkable ( approximately 78%) loss of intraepidermal nerve fibers. They also had increased sorbitol pathway activity in the sciatic nerve and increased nitrotyrosine and poly(ADP-ribose) immunofluorescence in the sciatic nerve, spinal cord, and dorsal root ganglion (DRG). Aldose reductase inhibition with fidarestat (16 mg . kg(-1) . d(-1)), administered to ob/ob mice for 6 weeks starting from 5 weeks of age, was associated with preservation of normal MNCV and SNCV and alleviation of thermal hypoalgesia and intraepidermal nerve fiber loss but not tactile allodynia. Sciatic nerve nitrotyrosine immunofluorescence and the number of poly(ADP-ribose)-positive nuclei in sciatic nerve, spinal cord, and DRGs of fidarestat-treated ob/ob mice did not differ from those in nondiabetic controls. In conclusion, the leptin-deficient ob/ob mouse is a new animal model that develops both large motor and sensory fiber and small sensory fiber PDN and responds to pathogenetic treatment. The results support the role for increased aldose reductase activity in functional and structural changes of PDN in type 2 diabetes.
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PMID:The leptin-deficient (ob/ob) mouse: a new animal model of peripheral neuropathy of type 2 diabetes and obesity. 1713 Apr 77

At least one of four diabetic patients is affected by distal symmetric polyneuropathy (DSP), which represents a major health problem, as it may present with partly excruciating neuropathic pain and is responsible for substantial morbidity, increased mortality, and impaired quality of life. Treatment is based on four cornerstones: (a) causal treatment aimed at (near)-normoglycemia, (b) treatment based on pathogenetic mechanisms, (c) symptomatic treatment, and (d) avoidance of risk factors and complications. Recent experimental studies suggest a multifactorial pathogenesis of diabetic neuropathy. From the clinical point of view it is important to note that, on the basis of these pathogenetic mechanisms, therapeutic approaches could be derived, some of which are currently being evaluated in clinical trials. Among these agents only alpha-lipoic acid is available for treatment in several countries and epalrestat in Japan. Although several novel analgesic drugs, such as duloxetine and pregabalin, have recently been introduced into clinical practice, the pharmacological treatment of chronic painful diabetic neuropathy remains a challenge for the physician. Individual tolerability remains a major aspect in any treatment decision. Epidemiological data indicate that not only increased alcohol consumption but also the traditional cardiovascular risk factors, such as hypertension, smoking, and visceral obesity, play a role in development and progression of diabetic neuropathy and, hence, need to be prevented or treated.
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PMID:Treatment of diabetic polyneuropathy: Update 2006. 1715 6

In most Western countries, diabetic nephropathy (DN) has become the single most common condition found in patients with end-stage renal disease (ESRD). This is to some extent due to better survival of diabetic patients with renal failure, but mostly due to the dramatic increase in the prevalence of type 2 diabetes. The majority of type 2 diabetic patients with renal failure suffer from nodular glomerulosclerosis (Kimmelstiel-Wilson); but ischemic nephropathy, irreversible acute renal failure (mostly acute on chronic) and diabetes co-existing with primary renal diseases are common as well. Classical DN evolves in a sequence of stages. After a period of glomerular hyperfiltration, increased urinary albumin excretion [microalbuminuria (MA)] i.e. 30-300 mg/day or 20 - 200 microg/minute indicates the onset of overt DN. Risk factors for development of DN are positive family history, hyperglycemia in the mother during pregnancy, high blood pressure, obesity and insulin resistance. Poor glycemic control (HbAlc) and elevated systolic blood pressure (> 135 mm Hg) interact in enhancing the risk of DN. Proteinuria and smoking are major promoters of progression. The risk of onset of microalbuminuria can be reduced by lowering of blood pressure and specifically by blockade of the renin angiotensin system (RAS). In patients with established DN, the target systolic blood pressure should be <130 mm Hg and RAS blockade is obligatory. Treating all cardiovascular risk factors is a high priority. Antihypertensive management is rendered difficult by extreme volume sensitivity, pronounced activation of the RAS and autonomic neuropathy. Cardiac events are excessively frequent, glycemic control becomes difficult and autonomic diabetic neuropathy with gastroparesis and diabetic foot are additional problems. Hemodialysis or continuous ambulatory peritoneal dialysis should be started relatively early. In the absence of contraindications, transplantation (renal transplantation, combined kidney/pancreas transplantation or pancreas after kidney transplantation) is the treatment of choice.
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PMID:Diabetic nephropathy. 1718 81

In the last two decades, diabetes mellitus has reached epidemic proportions in the United States. Most of the recent increase in prevalence of diabetes involves type 2 disease and is a result of an alarming increase in prevalence of obesity, although type 1 diabetes may also be on the rise. Advances in treatment have essentially eliminated ketoacidosis as a cause of death and led to better glycemic control than ever before. Consequently, diabetics now live a longer life, allowing many of them to develop the chronic complications of the disease. Here we review the evidence that a maladaptive response to hyperglycemia contributes to diabetic neuropathy, a major microvascular complication. We postulate that the same response may also be the culprit for the other chronic complications of diabetes.
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PMID:Chronic diabetic complications: the body's adaptive response to hyperglycemia gone awry? 1852 85

The melanocortins (alpha, beta and gamma-melanocyte-stimulating hormones: MSHs; adrenocorticotrophic hormone: ACTH), a family of pro-opiomelanocortin (POMC)-derived peptides having in common the tetrapeptide sequence His-Phe-Arg-Trp, have progressively revealed an incredibly wide range of extra-hormonal effects, so to become one of the most promising source of innovative drugs for many, important and widespread pathological conditions. The discovery of their effects on some brain functions, independently made by William Ferrari and David De Wied about half a century ago, led to the formulation of the term "neuropeptide" at a time when no demonstration of the actual production of peptide molecules by neurons, in the brain, was still available, and there were no receptors characterized for these molecules. In the course of the subsequent decades it came out that melanocortins, besides inducing one of the most complex and bizarre behavioural syndromes (excessive grooming, crises of stretchings and yawnings, repeated episodes of spontaneous penile erection and ejaculation, increased sexual receptivity), play a key role in functions of fundamental physiological importance as well as impressive therapeutic effects in different pathological conditions. If serendipity had been an important determinant in the discovery of the above-mentioned first-noticed extra-hormonal effects of melanocortins, many of the subsequent discoveries in the pharmacology of these peptides (feeding inhibition, shock reversal, role in opiate tolerance/withdrawal, etc.) have been the result of a planned research, aimed at testing the "pro-nociceptive/anti-nociceptive homeostatic system" hypothesis. The discovery of melanocortin receptors, and the ensuing synthesis of selective ligands with agonist or antagonist activity, is generating completely innovative drugs for the treatment of a potentially very long list of important and widespread pathological conditions: sexual impotence, frigidity, overweight/obesity, anorexia, cachexia, haemorrhagic shock, other forms of shock, myocardial infarction, ischemia/reperfusion-induced brain damage, neuropathic pain, rheumathoid arthritis, inflammatory bowel disease, nerve injury, toxic neuropathies, diabetic neuropathy, etc. This review recalls the history of these researches and outlines the pharmacology of the extra-hormonal effects of melanocortins which are produced by an action at the brain level (or mainly at the brain level). In our opinion the picture is still incomplete, in spite of being already so incredibly vast and complex. So, for example, several of their effects and preliminary animal data suggest that melanocortins might be of concrete effectiveness in one of the areas of most increasing concern, i.e., that of neurodegenerative diseases.
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PMID:Brain effects of melanocortins. 1899 99


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