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

Severe obesity is associated with multiple comorbidities and is refractory to dietary management with or without behavioral or drug therapies. There are a number of surgical procedures for the treatment of morbid obesity, including purely gastric restrictive, a combination of malabsorption and gastric restriction or primary malabsorption. The purely gastric restrictive procedures, including vertical banded gastroplasty and laparoscopic adjustable silicone gastric banding, do not provide adequate weight loss. African-American patients do especially poorly after the banding procedure with the loss of only 11% of excess weight in one study. Gastric bypass (GBP) is associated with the loss of 66% of excess weight at 1 to 2 years after surgery, 60% at 5 years and 50% at 10 years. For unknown reasons, African-American patients lose significantly less weight than Caucasians after GBP. There is a risk of micronutrient deficiencies after GBP, including iron deficiency anemia in menstruating women, vitamin B12, and calcium deficiencies. Prophylactic supplementation of these nutrients is necessary. Recurrent vomiting after bariatric surgery may be associated with a severe polyneuropathy and must be aggressively treated with endoscopic dilatation before this complication is allowed to develop. The malabsorptive procedures include the partial biliopancreatic bypass (BPD) and BPD with duodenal switch (BPD/DS). The BPD appears to cause severe protein-calorie malnutrition in American patients; the BPD/DS may be associated with less malnutrition. Weight loss failure after GBP does not respond to tightening a dilated gastrojejunal stoma or reducing the size of the gastric pouch. These patients may require conversion to a malabsorptive distal GBP, similar to the BPD. However, because of the risk of severe protein-calorie malnutrition and calcium deficiency BPD should be reserved for patients with severe obesity comorbidity. The risk of death following bariatric surgery is between 1% and 2% in most series but is significantly higher in patients with respiratory insufficiency of obesity. In most patients, surgically induced weight loss will correct hypertension, type II diabetes mellitus, sleep apnea, obesity hypoventilation syndrome, gastroesophageal reflux, venous stasis disease, urinary incontinence, female sexual hormone dysfunction, pseudotumor cerebri, degenerative joint disease pains, as well as improved self-image and employability.
 ...
PMID:Bariatric surgery for severe obesity. 1185 Dec 1

Diabetic lumbosacral radiculoplexus neuropathy (DLRPN) (also called diabetic amyotrophy) is a well-recognized subacute, painful, asymmetric lower-limb neuropathy that is associated with weight loss and type II diabetes mellitus. Nondiabetic lumbosacral radiculoplexus neuropathy (LRPN) has received less attention. Comparison of large cohorts with DLRPN and LRPN demonstrated that age at onset, course, type and distribution of symptoms and impairments, laboratory findings, and outcomes are similar. Both conditions are lumbosacral radiculoplexus neuropathies that are associated with weight loss and begin focally with pain but that evolve into widespread, bilateral paralytic disorders. Although both are monophasic illnesses, patients have prolonged morbidity from pain and weakness, and many patients become wheelchair-dependent. Although motor-predominant, there is unequivocal evidence that autonomic and sensory nerves are also involved. Cutaneous nerves from patients with DLRPN and LRPN show pathological evidence of ischemic injury (multifocal fiber loss, perineurial thickening and degeneration, neovascularization, microfasciculation, and swollen axons with accumulated organelles) and microvasculitis (mural and perivascular inflammation, separation and fragmentation of mural smooth muscle layers of microvessels and hemosiderin-laden macrophages). Controlled trials with immune-modulating therapies in DLRPN are in progress, and preliminary data suggest that such therapy may be beneficial in LRPN. It is likely that DLRPN and LRPN are immune-mediated neuropathies that should be separated from chronic inflammatory demyelinating polyneuropathy and from systemic necrotizing vasculitis.
 ...
PMID:Diabetic and nondiabetic lumbosacral radiculoplexus neuropathies: new insights into pathophysiology and treatment. 1193 65

Angiotensin-converting enzyme (ACE) gene polymorphism is thought to be a potent risk factor for nephropathy and retinopathy in diabetes. We investigated the association between polyneuropathy and gene polymorphisms of both the ACE insertion/deletion (I/D) and angiotensinogen (AGT) M235T genes in 84 type 2 diabetic patients without macroalbuminuria (21 with polyneuropathy and 63 without). ACE genotype distribution did not differ significantly between patients with and without polyneuropathy, but the frequency of the I allele was significantly higher in those with polyneuropathy than in those without. In contrast, neither the genotype distribution nor the allele frequencies of the AGT gene differed between the two groups. In logistic regression analysis using a D-additive model, the D allele had a protective effect on polyneuropathy (odds ratio [OR], 0.34; 95% confidence interval [CI], 0.13-0.88). A D-dominant model hypothesis also gave a significant OR (0.28; 95% CI, 0.09-0.90). ACE I/D polymorphism, but not AGT M235T polymorphism, may affect polyneuropathy development in type 2 diabetes without macroalbuminuria.
 ...
PMID:Angiotensin-converting enzyme insertion/deletion polymorphism and polyneuropathy in type 2 diabetes without macroalbuminuria. 1244 16

Diabetic sensorimotor polyneuropathy (DSP) remains the most common microvascular complication of both type I and type 2 diabetes, and poses a unique set of management challenges in the prevention of foot complications. Although different quantitative tests are available, the preliminary diagnosis of DSP can be reliably made using simple and rapid screening tests in the family physician's office or in the diabetes clinic. The Semmes-Weinstein 10-g monofilament examination is a popular, simple clinical modality for the prediction of early DSP, foot ulceration, and amputation, and, in turn, a predictor of mortality in patients with diabetes. The management of DSP is centered on optimal glycemic control, diligent foot care, and pain control as a means of preventing the progression of DSP and reducing the morbidity associated with foot complications.
 ...
PMID:Diagnosis and management of diabetic neuropathy. 1264 56

R-(+)-alpha-lipoic acid (R-LA) is the naturally occurring enantiomer of LA. It is a strong antioxidant and cofactor of key metabolic enzyme complexes catalyzing the decarboxylation of alpha-keto acids. Racemic LA (rac-LA) has shown promise in treating diabetic polyneuropathy, and some studies suggest that it improves glucose homeostasis in patients with type 2 diabetes. We examined the effects of R-LA on pyruvate metabolism and free fatty acid (FFA) oxidation in primary cultured hepatocytes isolated from 24-hour fasted rats. After overnight culture in serum-free medium, cells were pre-exposed to R-LA for 3 hours before assays. R-LA (25 to 200 micromol/L) significantly increased pyruvate oxidation ( approximately 2-fold at the highest dose tested) measured as (14)CO(2) production from [1-(14)C]pyruvate by the cells over 1 hour post-treatment. These effects correlated with proportional, significant increases in the activation state of the pyruvate dehydrogenase (PDH) complex. R-LA treatment inhibited glucose production from pyruvate by approximately 50% at 50 micromol/L R-LA and approximately 90% at 200 micromol/L. Palmitate oxidation was measured in hepatocytes cultured in the presence of albumin and physiological (0.1 mmol/L) or high (1.5 mmol/L) concentrations of FFA. The latter markedly enhanced FFA oxidation. R-LA treatment significantly inhibited FFA oxidation in both media, but was more effective in high FFA, where it reduced FFA oxidation by 48% to 82% at 25 to 200 micromol/L, respectively. Identical doses of R-LA did not affect FFA oxidation by L6 myotubes (a cell culture model for skeletal muscle) in either high or low FFA medium, but enhanced pyruvate oxidation. In conclusion, 3-hour exposure of primary cultured rat hepatocytes to R-LA at therapeutically relevant concentrations increased pyruvate oxidation, apparently by activation of the PDH complex, and decreased gluconeogenesis and FFA oxidation. These features may prove useful in the control of type 2 diabetes.
 ...
PMID:Effect of R(+)alpha-lipoic acid on pyruvate metabolism and fatty acid oxidation in rat hepatocytes. 1476 67

In the history of diabetes, chlorpropamide alcohol flushing test (CPAF) was a big topic in the 1970s to 1980s. Alcohol tolerance after chlorpropamide has prognostic significance, with the intolerant group (CPAF-positive group) being less prone to develop vascular complication than the tolerant group (CPAF-negative group). A mechanism of CPAF has been regarded as the inhibition of aldehyde dehydrogenase 2 (ALDH2) by an N-alkyl-substituted derivative of chlorpropamide, and the expression of these mutations of ALDH2 and alcohol dehydrogenase 2 (ADH2) could determine the alcohol tolerance among the Japanese population. Therefore, we hypothesized that expression of different ALDH2 and ADH2 polymorphisms may induce differences in vascular complications in diabetes and conducted two studies. The first study (study 1) was to determine the association of ALDH2/AHD2 polymorphism with diabetic complications. To know the association of ALDH2/AHD2 polymorphism with diabetic vasculopathy and neuropathy, a total of 158 patients with type 2 diabetes were divided into four groups on the basis of ALDH2 "activity" and ADH2 "superactivity." The frequency of proteinuria and the percentage of proliferative retinopathy among the patients with retinopathy was higher in those with active ALDH2 and superactive ADH2. We speculated that protein kinase C isoforms up-regulated by 4-hydroxynonenal that was detoxified by ALDH2 and ADH2 may account for the long-term development of diabetic nephropathy and severe retinopathy. As for neuropathy, the frequency of symptomatic neuropathy was higher in patients with inactive ALDH2 and usual ADH2. We speculate that increased tissue levels of toxic aldehyde could result from inactive ALDH2 and usual ADH2 expression, which results in the increased level of reactive aldehyde in sensory neuron pathway, thereby causing symptomatic polyneuropathy.
 ...
PMID:ALDH2/ADH2 polymorphism associated with vasculopathy and neuropathy in type 2 diabetes. 1531 96

The aim of this study was to examine the efficacy and safety of duloxetine, a balanced and potent dual reuptake inhibitor of serotonin and norepinephrine, in the management of diabetic peripheral neuropathic pain. Serotonin and norepinephrine are thought to inhibit pain via descending pain pathways. In a 12-week, multicenter, double-blind study, 457 patients experiencing pain due to polyneuropathy caused by Type 1 or Type 2 diabetes mellitus were randomly assigned to treatment with duloxetine 20 mg/d (20 mg QD), 60 mg/d (60 mg QD), 120 mg/d (60 mg BID), or placebo. The diagnosis was confirmed by a score of at least 3 on the Michigan Neuropathy Screening Instrument. The primary efficacy measure was the weekly mean score of the 24-h Average Pain Score, which was rated on an 11-point (0-10) Likert scale (no pain to worst possible pain) and computed from diary scores between two site visits. Duloxetine 60 and 120 mg/d demonstrated statistically significant greater improvement compared with placebo on the 24-h Average Pain Score, beginning 1 week after randomization and continuing through the 12-week trial. Duloxetine also separated from placebo on nearly all the secondary measures including health-related outcome measures. Significantly more patients in all three active-treatment groups achieved a 50% reduction in the 24-h Average Pain Score compared with placebo. Duloxetine treatment was considered to be safe and well tolerated with less than 20 percent discontinuation due to adverse events. Duloxetine at 60 and 120 mg/d was safe and effective in the management of diabetic peripheral neuropathic pain.
 ...
PMID:Duloxetine vs. placebo in patients with painful diabetic neuropathy. 1592 94

Diabetic neuropathy is a debilitating disorder that occurs in nearly 50 percent of patients with diabetes. It is a late finding in type 1 diabetes but can be an early finding in type 2 diabetes. The primary types of diabetic neuropathy are sensorimotor and autonomic. Patients may present with only one type of diabetic neuropathy or may develop combinations of neuropathies (e.g., distal symmetric polyneuropathy and autonomic neuropathy). Distal symmetric polyneuropathy is the most common form of diabetic neuropathy. Diabetic neuropathy also can cause motor deficits, silent cardiac ischemia, orthostatic hypotension, vasomotor instability, hyperhidrosis, gastroparesis, bladder dysfunction, and sexual dysfunction. Strict glycemic control and good daily foot care are key to preventing complications of diabetic neuropathy.
 ...
PMID:Evaluation and prevention of diabetic neuropathy. 1595 41

Feline diabetes mellitus (FDM) closely resembles human type 2 diabetes mellitus (T2DM) in many respects including clinical, physiological, and pathological features of the disease. These features include age of onset of FDM in middle age, association with obesity, residual but declining insulin secretion, development of islet amyloid deposits, loss of approximately 50% of beta-cell mass, and development of complications in several organ systems including peripheral polyneuropathy and retinopathy. Many of the pathological aspects of the disease are also experimentally inducible, facilitating study of the pathogenesis of these lesions. Physiological aspects of FDM and obesity are also well studied in the cat and provide an excellent basis for comparative studies of human T2DM. The relatively short generation time of cats along with breed predispositions to development of FDM may allow for more rapid screening and identification of genetic markers for diabetes susceptibility. FDM, in both spontaneous and inducible forms, therefore provides a good animal model of human T2DM and may provide additional insights into the pathogenesis of this important condition.
 ...
PMID:Feline models of type 2 diabetes mellitus. 1680 98

Although the postural stability of diabetic patients is affected in the presence of polyneuropathy, it has been suggested that diabetes per se has no effect on balance control during quiet standing. However, recent studies have reported muscular mechanical deficits in patients with type 2 diabetes (T2D) that may be highlighted during a more destabilizing task than quiet standing. Therefore, the objective of this study was to compare non-diabetic and T2D subjects during a modified version of the functional reach (FR) test in order to discriminate differences in postural control associated with diabetes per se. Thirty subjects (15 non-diabetic and 15 T2D) were requested to stand on a force platform and to perform the FR test. Center of pressure velocity (V(COP)), root-mean-square (RMS) amplitude and range of the COP were calculated in the anterior-posterior direction during three specific periods of the FR performance: namely "before", "on-going" and "after". No significant difference between the non-diabetic subjects and the T2D subjects was found for the FR performance. However, T2D subjects had significantly higher V(COP), RMS and range of COP displacements for the "after" period compared to the non-diabetic group (p<0.05). These results suggest that T2D subjects without peripheral neuropathy may have difficulties regaining their stability after a self-initiated reaching task. Therefore, diabetes mellitus per se, could have a direct effect on postural control during standing after a self-induced forward reaching movement.
 ...
PMID:Postural control following a self-initiated reaching task in type 2 diabetic patients and age-matched controls. 1687 95


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