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)

We recently published the results of the Steno-2 study, which evaluated the benefits of intensified integrated behavior modification and targeted polypharmacy. The results provide abundant evidence that an ambitious treatment strategy is superior to a conventional one. The study involved 160 high-risk type 2 diabetic patients with microalbuminuria-a strong risk factor of both macrovascular and microvascular complications-aged 55.1 years, who were randomly assigned to a conventional or an intensive, multifactorial intervention for a period of 7.8 years. In the intensive group, a stepwise treatment plan was adopted involving both continuous lifestyle education and motivation and an ambitious goal-oriented pharmacological treatment of known modifiable risk factors. The conventional group was treated in accordance with national guidelines for type 2 diabetes with less stringent goals. The specific significant group differences in the degree of change in key clinical and biochemical variables at the end of the study were (in the intensive group): lower systolic and diastolic blood pressures, hemoglobin A(1c) (HbA(1c)), fasting serum total and low-density lipoprotein (LDL) cholesterol, fasting serum triglycerides, and 24-hour urine albumin excretion, as well as increased carbohydrate and decreased fat intake as percentage of total energy. There was no difference in weight gain between groups during follow-up and no other major side effects were reported. The primary end point was a macrovascular outcome: a composite of death from cardiovascular causes, nonfatal myocardial infarction, coronary artery bypass grafting, percutaneous coronary intervention, nonfatal stroke, amputation for ischemia, or vascular surgery for peripheral arterial atherosclerosis. The differences between groups in surrogate end points translated into the following significant group differences in final clinical end points: 44% of patients in the conventional group had a cardiovascular event compared with 24% in the intensive group, ie, a relative risk reduction of about 50%. Also, the relative risk of nephropathy, retinopathy, and autonomic neuropathy (secondary end points) was diminished by about 60% in the intensively treated group. In conclusion, an intensified and goal-oriented multipronged approach to the treatment of type 2 diabetes reduces cardiovascular events, as well as nephropathy, retinopathy, and autonomic neuropathy, by about half. The challenge is to ensure that this experience is widely adopted in daily practice.
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PMID:Intensified multifactorial intervention and cardiovascular outcome in type 2 diabetes: the Steno-2 study. 1293 35

All cells must maintain a high ratio of cellular ATP:ADP to survive. Because of the adenylate kinase reaction (2ADP <--> ATP + AMP), AMP rises whenever the ATP:ADP ratio falls, and a high cellular ratio of AMP:ATP is a signal that the energy status of the cell is compromised. The AMP-activated protein kinase (AMPK) is the downstream component of a protein kinase cascade that is switched on by a rise in the AMP:ATP ratio, via a complex mechanism that results in an exquisitely sensitive system. AMPK is switched on by cellular stresses that either interfere with ATP production (e.g. hypoxia, glucose deprivation, or ischemia) or by stresses that increase ATP consumption (e.g. muscle contraction). It is also activated by hormones that act via Gq-coupled receptors, and by leptin and adiponectin, via mechanisms that remain unclear. Once activated, the system switches on catabolic pathways that generate ATP, while switching off ATP-consuming processes that are not essential for short-term cell survival, such as the synthesis of lipids, carbohydrates, and proteins. The AMPK cascade is the probable target for the antidiabetic drug metformin, and current indications are that it is responsible for many of the beneficial effects of exercise in the treatment and prevention of type 2 diabetes and the metabolic syndrome.
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PMID:Minireview: the AMP-activated protein kinase cascade: the key sensor of cellular energy status. 1296 15

Systemic hypertension and type 2 diabetes mellitus are major risk factors for myocardial infarction. Yet, glucose intolerance, a prelude stage to type 2 diabetes, is associated with reduced infarct size. Since chronic hypertension adversely affects the myocardium, we tested the hypothesis that the coexistence of systemic hypertension and glucose intolerance reverses the cardioprotection associated with impaired glucose tolerance. Hearts from 9-month-old animals were subjected to a 40-minute occlusion of the left coronary artery followed by 2 hours of reperfusion. Before ischemia, similar values for the four experimental groups were observed for the coronary flow, heart rate, and maximum ventricular pressure. During the course of the ischemia-reperfusion insult, the two hypertensive groups displayed greater reductions in contractility than their normotensive counterparts. Infarct size was lower in the normotensive glucose-intolerant rat than in the normotensive control rat. Surprisingly, the hypertrophied hearts of the hypertensive and hypertensive glucose-intolerant rats displayed reduced infarct size (P<0.05). However, raising the afterload pressure from 100 to 160 cm H2O increased infarct size in the two hypertensive groups. This narrowed the differential between the hypertensive glucose-intolerant (160 cm H2O) and the normotensive control (100 cm H2O) rats. Nonetheless, at the higher afterload pressure, infarct size was less in the hypertensive glucose-intolerant rats than in their hypertensive counterparts. In conclusion, the impairment in contractile function despite the reduction in infarct size underscores the increased susceptibility of the hypertrophied, hypertensive heart to ischemic injury. Furthermore, exacerbation of cell death at elevated afterload pressure indicates the potential benefit of aggressive antihypertensive therapy.
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PMID:Effect of hypertension and hypertension-glucose intolerance on myocardial ischemic injury. 1455 78

The prevalence of diabetes and resultant complications continues to increase in many countries, including Brazil. A 1-day, multicenter descriptive study involving people with type 2 diabetes was conducted 1) to identify and describe indicators of foot neuropathy and ischemia and examine their relationship, and 2) to examine the relationship between existing risk factors and patient demographic and clinical variables. Seventy-nine (79) patients with an average age of 60.9 years (SD = 13.28) participated in the study. After obtaining a history, the feet of all participants were examined (assessment, palpation, and sensitivity tests using a 128-Hz tuning fork and a 10-g Semmes-Weinstein monofilament). The majority of study participants were women (57%) and the average length of time since diagnosis of diabetes for all participants was 7.76 years (SD = 6.69). The majority of participants were found to have neuropathic and ischemic changes, risk factors for the development of ulcers, or both. Thirty-one patients (42.47%) had cramps, 29 reported numbness (39.73%), 31 (39.24%) lacked sensory perception to the monofilament, 26 (35.62%) experienced tingling, 16 had paresthesia (22.86%), 15 (19.99%) lacked vibratory perception to the tuning fork, 14 felt burning (19.44%), and six had hyperesthesia (10.34%). Certain neuropathic and ischemic changes, as well as some risk factors, were observed more often in male and aged patients, respectively. Men were significantly more likely than women to lack vibratory perception or posterior tibial pulse and to have calluses and an ingrown toenail. Claw toe, lack of sensory perception to the monofilament, lack of posterior tibial pulse, lack of hair, reduced capillary filling, onychomycosis, ingrown toenail, and varices were significantly more common in older than in younger study participants. These results reinforce the importance of regular preventive foot examinations of patients with type 2 diabetes mellitus and confirm that nursing foot care can easily be expanded to include these much-needed assessments.
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PMID:Neuropathic and ischemic changes of the foot in Brazilian patients with diabetes. 1463 64

The aim of this study was to determine whether the transition from insulin resistance to hyperglycemia in a model of type 2 diabetes leads to intrinsic changes in the myocardium that increase the sensitivity to ischemic injury. Hearts from 6-, 12-, and 24-wk-old lean (Control) and obese Zucker diabetic fatty (ZDF) rats were isolated, perfused, and subjected to 30 min of low-flow ischemia (LFI) and 60 min of reperfusion. At 6 wk, ZDF animals were insulin resistant but not hyperglycemic. By 12 wk, the ZDF group was hyperglycemic and became progressively worse by 24 wk. In spontaneously beating hearts rate-pressure product (RPP) was depressed in the ZDF groups compared with age-matched Controls, primarily due to lower heart rate. Pacing significantly increased RPP in all ZDF groups; however, this was accompanied by a significant decrease in left ventricular developed pressure. There was also greater contracture during LFI in the ZDF groups compared with the Control group; surprisingly, however, functional recovery upon reperfusion was significantly higher in the diabetic 12- and 24-wk ZDF groups compared with age-matched Control groups and the 6-wk ZDF group. This improvement in recovery in the ZDF diabetic groups was independent of substrate availability, severity of ischemia, and duration of diabetes. These data demonstrate that, although the development of type 2 diabetes leads to progressive contractile and metabolic abnormalities during normoxia and LFI, it was not associated with increased susceptibility to ischemic injury.
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PMID:Onset of diabetes in Zucker diabetic fatty (ZDF) rats leads to improved recovery of function after ischemia in the isolated perfused heart. 1472 22

Greater myocardial injury in response to ischemia/ reperfusion (I/R) and increased incidence of congestive heart failure and death in noninsulin-dependent diabetes mellitus, or type 2 diabetes, patients has been clearly identified. Thiazolidinediones (TZDs), peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists, act as insulin sensitizers and are a novel class of oral antidiabetic drugs. An emerging body of evidence, mainly from preclinical studies, suggest that TZDs protect the heart from acute I/R injury and also might attenuate cardiac remodeling and heart failure. The mechanisms involved in this cardioprotection by TZDs are multi-factorial and not completely understood. These novel activities of TZDs could benefit type 2 diabetes patients and offer benefits beyond glycemic control. This new knowledge about the cardioprotective effects of TZDs is still limited, and more investigations, especially clinical studies, are required.
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PMID:Cardioprotective effects of thiazolidinediones, peroxisome proliferator-activated receptor-gamma agonists. 1474 40

Endothelial dilator function is impaired in people with type 2 diabetes mellitus (T2DM). Prior research indicates that this can be improved with intravenous administration of ascorbate or L-arginine, but whether these agents have this effect when administered by the clinically practical oral route is unknown. To investigate this question, 10 premenopausal women with T2DM and 10 healthy, premenopausal, non-diabetic women received, in random sequence, a 1-week administration of oral L-arginine (9 g daily) or vitamins E (1800 mg) and C (1000 mg) with an intervening 1-week washout period. Flow-mediated brachial artery dilation (FMD) was measured by ultrasonography and forearm blood flow was measured by plethysmography before and following blood pressure cuff-induced forearm ischemia before and after each week of treatment. At baseline, the women with T2DM had lesser FMD responses (0.028 +/- 0.006 cm vs 0.056 +/- 0.008 cm, p < 0.05). Post-ischemic forearm hyperemia was reduced at baseline in T2DM compared with controls (16.4 +/- 1.8 vs 26.0 +/- 1.4 ml 100 ml(-1) min(-1), p < 0.05). Administration of L-arginine caused a 50 +/- 12% increase in FMD in T2DM (p < 0.05) and raised post-ischemic forearm blood flow by 29 +/- 8% (p < 0.05). No significant changes were seen in controls. Administration of vitamins E and C in women with T2DM produced an increase in the brachial artery diameter response of 79 +/- 15% (p < 0.05), but did not significantly increase the hyperemic blood flow response (p = NS). No significant changes in the responses of controls from pre to post vitamin administration were observed. We concluded that administration of two types of oral agents improved measures of endothelial function in people with T2DM.
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PMID:Oral L-arginine and vitamins E and C improve endothelial function in women with type 2 diabetes. 1498 57

Sulfonylureas, which have evolved through two generations since their introduction nearly 50 years ago, remain the most frequently prescribed oral agents for treatment of patients with type 2 diabetes mellitus. Glyburide, glipizide, and glimepiride, the newest sulfonylureas, are as effective at lowering plasma glucose concentrations as first-generation agents but are more potent, better tolerated, and associated with a lower risk of adverse effects. Differences in their binding affinity to the beta-cell sulfonylurea receptor have been described, with preservation of cardioprotective responses to ischemia with glimepiride. Clinical studies have shown glimepiride to be safe and effective in reducing fasting and postprandial glucose levels, as well as glycosylated hemoglobin concentrations, with dosages of 1-8 mg/day. In comparative trials, glimepiride was as effective in lowering glucose levels as glyburide and glipizide, but glimepiride was associated with a reduced likelihood of hypoglycemia and a smaller increase in fasting insulin and C-peptide levels than glyburide, and a more rapid lowering of fasting plasma glucose levels than glipizide. Glimepiride also improves first-phase insulin secretion, which plays an important role in reducing postprandial hyperglycemia. Insulin secretagogues, specifically glimepiride, merit consideration as first-line therapy for patients with type 2 diabetes.
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PMID:Sulfonylurea treatment of type 2 diabetes mellitus: focus on glimepiride. 1516 95

This study evaluated the usefulness of thallium-201 muscle perfusion scan (Tl-201 muscle scan) to investigate perfusion reserve in the lower limbs of asymptomatic Type 2 diabetic patients without peripheral ischemia findings. Tl-201 muscle scan was carried out in 36 diabetic male patients with Type 2 diabetes mellitus of more than 10 years in duration who had no evidence of peripheral arterial disease in their history, physical examination, or Doppler ultrasonography. A control group consisted of 24 healthy age-matched nondiabetic men. Each subject flexed their right foot maximally both dorsally and plantar 60 times. In the middle of this exercise, 2mCi Tl-201 was injected intravenously. Three minutes after the injection, a posterior image of both calves was obtained using a gamma camera. Rectangular regions of interest (ROIs) were symmetrically drawn over both calves. The total count (Ct) in the resting calf was subtracted from the Ct in the exercising calf, and the percentage increase, termed the perfusion reserve, was determined. A significant difference was found between the perfusion reserves of the Type 2 diabetic patients and control groups (70.2+/-10.7% and 98.6+/-9.4%, respectively; P<.05). In conclusion, the perfusion reserve in the lower limb muscles in Type 2 diabetic patients may be measured by Tl-201 muscle perfusion scan.
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PMID:Usefulness of thallium-201 muscle perfusion scan to investigate perfusion reserve in the lower limbs of Type 2 diabetic patients. 1520 43

Aging and diabetes in women increase their susceptibility to myocardial ischemic injury, but the cellular mechanisms involved are not understood. Consequently, we studied the influence of gender on cardiac insulin resistance and ischemic injury in the aging of Goto-Kakizaki (GK) rat, a model of type 2 diabetes. Male and female GK rats had heart/body weight ratios 29% (P < 0.0001) and 53% (P < 0.0001) higher, respectively, than their sex-matched controls, with the female GK rat hearts significantly more hypertrophied than the male (P < 0.001). Glucose transporter (GLUT) 1 protein levels were the same in all hearts, but GLUT4 protein levels were 28% lower (P < 0.01) in all GK rat hearts compared with their sex-matched controls. In isolated, perfused hearts, insulin-stimulated (3)H-glucose uptake rates were decreased by 23% (P < 0.05) and 40% (P < 0.05) in male and female GK rat hearts, respectively, compared with their controls, with the female significantly more insulin resistant than the male GK rat hearts (P < 0.05). Protein kinase B protein levels and insulin-stimulated phosphorylation were the same in all hearts. During low-flow ischemia, glucose uptake was 59% lower (P < 0.001) in female, but the same as controls in male, GK rat hearts. Consequently, recovery of contractile function during reperfusion was 30% lower (P < 0.05) in female, but the same as controls in male GK rat hearts. We conclude that the aging female type 2 diabetic rat heart has increased insulin resistance and greater susceptibility to ischemic injury, than non-diabetic or male type 2 diabetic rat hearts.
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PMID:Gender differences in hypertrophy, insulin resistance and ischemic injury in the aging type 2 diabetic rat heart. 1527 24


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