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)

Alcohol influences glucose metabolism in several ways in diabetic patients as well as in non-diabetic patients. Since alcohol inhibits both gluconeogenesis and glycogenolysis, its acute intake without food may provoke hypoglycaemia, especially in cases of depleted glycogen stores and in combination with sulphonylurea. Consumed with a meal including carbohydrates, it is the preferred fuel, which may initially lead to somewhat higher blood glucose levels and hence an insulin response in type 2 diabetic patients. Depending on the nature of the carbohydrates in the meal, this may be followed by reactive hypoglycaemia. Moderate consumption of alcohol is associated with a reduced risk of atherosclerotic disorders. Diabetic patients benefit from this favourable effect as much as non-diabetic patients. Apart from effects on lipid metabolism, haemostatic balance and blood pressure, alcohol improves insulin sensitivity. This improvement of insulin sensitivity may also be responsible for the lower incidence of type 2 diabetes mellitus reported to be associated with light-to-moderate drinking. In case of moderate and sensible use, risks of disturbances in glycaemic control, weight and blood pressure are limited. Excessive intake of alcohol, however, may not only cause loss of metabolic control, but also annihilate the favourable effects on the cardiovascular system.
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PMID:Diabetes mellitus and alcohol. 1525 29

Nonalcoholic steatohepatitis (NASH) represents an advanced stage of fatty liver disease developed in the absence of alcohol abuse. Its increasing prevalence in western countries, the diagnostic difficulties by noninvasive tests, and the possibility of progression to advanced fibrosis and even cirrhosis make NASH a challenge for hepatologists. NASH is frequently associated with type 2 diabetes and the metabolic syndrome, and several genetic and acquired factors are involved in its pathogenesis. Insulin resistance plays a central role in the development of a steatotic liver, which becomes vulnerable to additional injuries. Several cyclic mechanisms leading to self-enhancement of insulin resistance and hepatic accumulation of fat have been recently identified. Excess intracellular fatty acids, oxidant stress, tumor necrosis factor-alpha, and mitochondrial dysfunction are causes of hepatocellular injury, thereby leading to disease progression and to the establishment of NASH. Intestinal bacterial overgrowth also plays a role, by increasing production of endogenous ethanol and proinflammatory cytokines. Therapeutic strategies aimed at modulating insulin resistance, normalizing lipoprotein metabolism, and downregulating inflammatory mediators with probiotics have promising potential.
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PMID:Approach to the pathogenesis and treatment of nonalcoholic steatohepatitis. 1527 42

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.
Alcohol Clin Exp Res 2004 Aug
PMID:ALDH2/ADH2 polymorphism associated with vasculopathy and neuropathy in type 2 diabetes. 1531 96

Postmenopausal women in Western societies are conscious of breast cancer as a potential cause of death and ill health, which they wish to avoid with the advice of their doctors. Yet many factors that predispose women to the development of cancer will have been laid down before the menopause, in their genetic makeup or during their adolescent years. Even in middle age it is important to take account of the intrinsic level of risk, and to give women advice tailored to their own individual risk level. This results from their family history, previous diseases such as benign breast disease, and previous treatment for breast cancer or Hodgkin's disease. For those at the highest level of risk, strategies will include regular screening, prophylactic mastectomy, and the use of chemoprevention agents, such as tamoxifen. These women should avoid hormone replacement therapy (HRT) and control their menopausal symptoms and osteoporosis through the use of other agents now available - venlafaxine for menopausal symptoms and bisphosphonates for osteoporosis. Raloxifene is an agent under trial that may be valuable for breast cancer control as well as for osteoporosis. Women at standard population risk will require less robust preventive strategies, which will include screening and lifestyle modification. Their decisions regarding HRT should now be modified by recent evidence of associated risks. Recent studies show that tibolone causes less mammographic density and has a lower relative risk of breast cancer than combined estrogen/progestogen preparations. There is limited evidence that controlling obesity, participating in exercise and adopting a diet low in fats and high in fruit and vegetables will alter risk at this age. These precautions will, however, reduce the risk of other diseases common in this age group, such as hypertension, heart disease, stroke, and type 2 diabetes mellitus. Alcohol, even in small amounts, is a risk factor for breast cancer. Given the cardioprotective effect of moderate alcohol intake, advice on alcohol must reflect the individual relative risk of cardiovascular disease and breast cancer. Personal risk assessment is relevant for all women. Screening and a healthy lifestyle are worthwhile approaches for all, with the more aggressive approaches such as chemoprevention and prophylactic surgery reserved for those who have substantially elevated levels of risk. Once the menopause has passed, screening is probably the most effective evidence-based tool for breast cancer control by early diagnosis.
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PMID:Strategies for managing breast cancer risk after the menopause. 1533 Jun 77

Ginseng is a shade-loving perennial herb that is cultivated mainly in Korea, Japan, and China. The ginseng root has been used as a tonic remedy, and its antidiabetic activity has been demonstrated as early as 1920s. Although wild ginseng was anecdotally thought to be superior to cultivated ginseng as far as pharmacological properties were concerned, there have been no prior reports on the antidiabetic effect of wild ginseng. In this study, we investigated the preventative anti-diabetic and anti-obese effects of wild ginseng ethanol extract (WGEE). In the preventive experiment, WGEE co-administered with a high fat diet significantly inhibited body weight gain, fasting blood glucose, triglyceride, and free fatty acid levels in a dose dependent manner. WGEE-treated mice at doses of 250 and 500 mg/kg improved the insulin resistance index by 55% and 61% compared to the high fat diet (HFD) control, respectively. Diameters of white and brown adipocytes were also decreased by 62% and 46% in the WG500-treated group compared to those in HFD fed control mice. Taken together, WGEE has potential as a preventive agent for type 2 diabetes mellitus (and possibly obesity) and deserves clinical trial in the near future.
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PMID:Wild ginseng prevents the onset of high-fat diet induced hyperglycemia and obesity in ICR mice. 1535 9

Moderate alcohol consumption protects against type 2 diabetes and cardiovascular disease. Because humans spend most of their time in the postprandial state, we examined the effect of 15 g alcohol on postprandial metabolic factors in 20 postmenopausal women over 6 h. We measured 1) glucose, insulin, lipids, C-reactive protein, and adiponectin levels; 2) augmentation index by applanation tonometry; and 3) energy expenditure and substrate oxidation by indirect calorimetry. Subjects received low carbohydrate (LC; visits 1 and 2) and high carbohydrate (HC; visits 3 and 4) high fat meals with and without alcohol. Alcohol augmented the postprandial increment in insulin (P = 0.07) and reduced the postprandial increment in glucose (P = 0.04) after the LC meal only. Triglycerides were increased by alcohol after the LC (P = 0.002) and HC (P = 0.008) meals. Total and high-density lipoprotein cholesterol, fatty acids, and total adiponectin responses were unaffected. C-reactive protein levels decreased postprandially; reductions were enhanced by alcohol after the HC meal, but were attenuated after the LC meal. Postprandial reductions in the augmentation index were increased by alcohol after the LC meal only (P = 0.007). Alcohol enhanced the postprandial increase in energy expenditure 30-60 min after the LC meal (increase, 373 +/- 49 vs. 236 +/- 32 kcal/d; P = 0.02) and HC meal (increase, 362 +/- 36 vs. 205 +/- 34 kcal/d; P = 0.0009), but suppressed fat and carbohydrate oxidation. Some of our findings may be mechanisms for lower diabetes and cardiovascular risks in moderate drinkers.
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PMID:Beneficial postprandial effect of a small amount of alcohol on diabetes and cardiovascular risk factors: modification by insulin resistance. 1552 27

The hormone insulin, which is produced in the pancreas, is an important regulator of blood sugar levels. In people with diabetes, the pancreas does not produce sufficient insulin (type 1 diabetes) or the body does not respond appropriately to the insulin (type 2 diabetes). Alcohol consumption by diabetics can worsen blood sugar control in those patients. For example, long-term alcohol use in well-nourished diabetics can result in excessive blood sugar levels. Conversely, long-term alcohol ingestion in diabetics who are not adequately nourished can lead to dangerously low blood sugar levels. Heavy drinking, particularly in diabetics, also can cause the accumulation of certain acids in the blood that may result in severe health consequences. Finally, alcohol consumption can worsen diabetes-related medical complications, such as disturbances in fat metabolism, nerve damage, and eye disease.
Alcohol Health Res World 1998
PMID:Consequences of alcohol use in diabetics. 1570 98

The turmeric (Curcuma longa L. rhizomes) EtOH extract significantly suppressed an increase in blood glucose level in type 2 diabetic KK-A(y) mice. In an in vitro evaluation, the extract stimulated human adipocyte differentiation in a dose-dependent manner and showed human peroxisome proliferator-activated receptor (PPAR)-gamma ligand-binding activity in a GAL4-PPAR-gamma chimera assay. The main constituents of the extract were identified as curcumin, demethoxycurcumin, bisdemethoxycurcumin, and ar-turmerone, which had also PPAR-gamma ligand-binding activity. These results indicate that turmeric is a promising ingredient of functional food for the prevention and/or amelioration of type 2 diabetes and that curcumin, demethoxycurcumin, bisdemethoxycurcumin, and ar-turmerone mainly contribute to the effects via PPAR-gamma activation.
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PMID:Hypoglycemic effects of turmeric (Curcuma longa L. rhizomes) on genetically diabetic KK-Ay mice. 1586 12

Findings obtained from numerous prospective cohort and case-control studies on alcohol consumption and pancreatic cancer risk have been inconsistent, with many confounding variables present in various investigations. However, heavy alcohol consumption has been known to be a major cause of chronic pancreatitis and a risk factor for type 2 diabetes mellitus, both of which are linked to pancreatic cancer. It has been established that an extensive normal interaction exists between the exocrine and endocrine pancreas, as well as in inflammatory processes and carcinogenesis. Alcohol and its metabolites (acetaldehyde and fatty acid ethyl esters) can alter metabolic pathways involved in the inflammatory response and carcinogenesis, and they are mediated by one or more of the following mechanisms: (1) premature activation of zymogens; (2) induction of the inflammatory response through activation of nuclear transcription factors, including nuclear factor-kappa and activation protein 1; (3) increased production of reactive oxygen species, resulting in oxidative DNA damage and altered effect of dietary antioxidants; (4) activation of pancreatic stellate cells, which leads to fibrosis; (5) gene mutation in enzymes related to cytochrome P450, glutathione S-transferase, aldehyde dehydrogenase, cationic trypsinogen, and pancreatic secretory trypsin inhibitor; (6) synergistic effects of ethanol and tobacco carcinogen on NNK [nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone] metabolism; and (7) dysregulation of proliferation and apoptosis. These various metabolic effects of alcohol can lead to or interact with other risk factors (genetic, dietary, environmental, and lifestyle factors) that result in acute and chronic pancreatitis and diabetes mellitus and, ultimately, affect the multistep process of carcinogenesis toward the development of pancreatic cancer.
Alcohol 2005 Apr
PMID:Alcohol and pancreatic cancer. 1605 82

Heavy alcohol consumption is an independent risk factor for type 2 diabetes. Although the exact mechanism by which alcohol contributes to the increased risk is unknown, impaired glucose disposal is a likely target. Insulin-stimulated glucose disposal in adipocytes is regulated by two separate and independent pathways, the PI3K pathway and the Cbl/TC10 pathway. Previous studies suggest that chronic ethanol feeding impairs insulin-stimulated glucose transport in adipocytes in a PI3K-independent manner. In search of potential targets of ethanol that would affect insulin-stimulated glucose transport, we investigated the effects of 4-wk ethanol feeding to male Wistar rats on the Cbl/TC10 pathway in isolated adipocytes. Chronic ethanol feeding inhibited insulin-stimulated cCbl phosphorylation compared with pair feeding. Insulin receptor and Akt/PKB phosphorylation were not affected by ethanol feeding. Chronic ethanol exposure also impaired cCbl and TC10 recruitment to a lipid raft fraction isolated from adipocytes by detergent extraction. Furthermore, chronic ethanol feeding increased the amount of activated TC10 and filamentous actin in adipocytes at baseline and abrogated the ability of insulin to further activate TC10 or polymerize actin. These results demonstrate that the impairment in insulin-stimulated glucose transport observed in adipocytes after chronic ethanol feeding to rats is associated with a disruption of insulin-mediated Cbl/TC10 signaling and actin polymerization.
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PMID:Decreased insulin-dependent glucose transport by chronic ethanol feeding is associated with dysregulation of the Cbl/TC10 pathway in rat adipocytes. 1610 61


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