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)

Approximately 7 million people in the United States are in jail, in prison, or on probation or parole, many as a result of drug-related offenses. Individuals who use opiates account for a significant minority of this population. Methadone maintenance treatment (MMT) of opiate addiction is highly effective in reducing drug use, drug-related criminal activity, and risk of human immunodeficiency virus transmission. Recently released inmates are at particularly high risk for overdose and disease transmission. Project MOD (Managing Opioid Dependency) provides services to eliminate logistical and financial barriers to MMT entry immediately on release from incarceration. Such programs provide a promising opportunity to facilitate reentry into the community, combat disease transmission, and reduce recidivism.
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PMID:Opiate replacement therapy at time of release from incarceration: Project MOD, a pilot program. 1731 18

It is imperative that the management of complex outpatient medical problems be taught using an apprentice system of education. The implementation of highly experienced and outcome successful "master physicians" to train outpatient practicing clinicians will provide a powerful frame of reference and a highly imitatable model on which clinicians can base their presentations of information and medications to patients with complex medical problems such as type 2 diabetes, cardiovascular disease, chronic pain, obesity, or tobacco addiction. Because doctors have always learned by observation, we must ensure that those who they observe will be "worth watching" and that those watched can provide skills of patient management currently not taught in the Flexnor-styled medical educational system, which effectively ended the apprentice system of training. The reintroduction of a carefully crafted apprentice system will foreseeably improve patient care and reduce morbidity, mortality, medical errors, and medical expenses.
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PMID:Proposal for a medical master class system of medical education for common complex medical entities. 1822 60

A lot of people, particularly young people begin smoking tobacco with the belief, that it is an effective means of body weight control. The decision to quit coming in a later stage of life is accompanied by the fear of gaining weight after stopping smoking. The mechanism through which nicotine may be an agent in the process of controlling body weight consists in increased energy expenditure of the organism and reduced appetite. However tobacco smoking is not an effective means of combating excessive weight. This is because it stimulates formation of abdominal adipose tissue, thus increasing the risk of type 2 diabetes and heart diseases. Therapy of tobacco addiction should be combined with diet counselling and promotion of physical activity, which will help to limit the increase of body weight.
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PMID:[Is tobacco smoking an effective means of body weight control--review of literature]. 1918 80

Rates of fructose consumption continue to rise nationwide and have been linked to rising rates of obesity, type 2 diabetes, and metabolic syndrome. Because obesity has been equated with addiction, and because of their evolutionary commonalities, we chose to examine the metabolic, hedonic, and societal similarities between fructose and its fermentation byproduct ethanol. Elucidation of fructose metabolism in liver and fructose action in brain demonstrate three parallelisms with ethanol. First, hepatic fructose metabolism is similar to ethanol, as they both serve as substrates for de novo lipogenesis, and in the process both promote hepatic insulin resistance, dyslipidemia, and hepatic steatosis. Second, fructosylation of proteins with resultant superoxide formation can result in hepatic inflammation similar to acetaldehyde, an intermediary metabolite of ethanol. Lastly, by stimulating the "hedonic pathway" of the brain both directly and indirectly, fructose creates habituation, and possibly dependence; also paralleling ethanol. Thus, fructose induces alterations in both hepatic metabolism and central nervous system energy signaling, leading to a "vicious cycle" of excessive consumption and disease consistent with metabolic syndrome. On a societal level, the treatment of fructose as a commodity exhibits market similarities to ethanol. Analogous to ethanol, societal efforts to reduce fructose consumption will likely be necessary to combat the obesity epidemic.
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PMID:Fructose: metabolic, hedonic, and societal parallels with ethanol. 2170 74

Since over-nutrition accelerates the development of obesity, progression to type 2 diabetes, and the associated co-morbidity and mortality, there has been a keen interest in therapeutic interventions targeting mechanisms that may curb appetite, increase energy expenditure or at least attenuate insulin resistance. Over the past decade, numerous peri-mitochondrial targets in the de novo lipid synthesis pathway have been linked to an increase in energy expenditure and the drug development industry has pursued the gene products involved as candidates to develop drugs against. The basis of this link, and specifically the premise that lowering tissue and cellular malonyl-CoA can increase energy expenditure, is scrutinised here. The argument presented is that fuel switching as effected by changes in cellular malonyl-CoA concentrations will not trigger the mitochondria to increase energy expenditure because: (1) an increase in beta-oxidation by lowering respiratory exchange ratio (indicative of the metabolic fuel consumed) does not equal an increase in energy expenditure (how rapidly fuel is consumed); (2) the ATP:oxygen ratios (i.e. ATP energy made:oxygen required for the reaction) are similar when metabolising lipids (2.8) vs glucose (3.0); (3) substrate availability (NEFA) does not drive energy expenditure in vivo; and (4) the availability of ADP in the mitochondrial matrix determines the rate of energy expenditure, not the availability of fuel to enter the mitochondrial matrix. To increase mitochondrial energy expenditure, work must be done (exercise) and/or the mitochondrial proton leak must be enhanced, both of which increase availability of ADP. In fact, despite the historic taboo of chemical uncoupling, this mechanism validated in humans is closest on task to increasing whole-body energy expenditure. Chemical uncoupling mimics the naturally occurring phenomenon of proton leak, accelerating the metabolism of glucose and lipids. However, it is completely non-genomic (i.e. the target is a location, not a gene product) and is not associated with addiction or mood alterations common to satiety agents. A significant hurdle for drug development is to discover a safe mitochondrial uncoupler and to formulate it potentially as a pro-drug and/or oral pump, to avoid the issue of overdosing experienced in the 1930s. The potential therapeutic impact of such a compound for an over-nutritioned patient population could be profound. If effective, the mitochondrial uncoupler mechanism could resolve many of the associated diseases such as type 2 diabetes, hypertension, obesity, depression, sleep apnoea, non-alcoholic steatohepatitis, insulin resistance and hyperlipidaemia, therefore becoming a 'disease-modifying therapy'.
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PMID:Targeting energy expenditure via fuel switching and beyond. 2095 61

As obesity, type 2 diabetes (T2DM) and the metabolic syndrome sweep across the research and the clinical landscape of medical care, effective pharmacologic remedies for the treatment of obesity have become imperative. The complexities of nutrient impact on neurotransmitter and endocrine modulating chemistry have become increasingly better characterized as have the basic neurochemical pathways that mediate their effects. Food addiction has emerged as an important phenomenon that may help to explain and improve our capabilities of rendering bench lab research into impactful clinical intervention. Against this challenging backdrop of current research and study we introduce the notion that food may in fact, itself, represent a type of drug. In this review chapter of food as a drug, we outline some of the emerging science that argues how proteins, carbohydrates and fats operating on three basic levels of organismic functioning may constitute the most powerful drugs we have available to effectuate weight loss or weight gain over time. In addition, certain foods may not only be more addictive than others, but may actually have a direct effect on pro-inflammatory mediators that determine both metabolic dysfunction as well as overall neuropsychiatric function and well-being.
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PMID:Food as a bariatric drug. 2149 82

'Globesity' is a descriptive term for the obesity epidemic now facing the U.S. and indeed, the world. Hyperphagia (i.e. overeating) can lead to metabolic syndrome which in turn can lead to Type 2 diabetes mellitus, heart disease, stroke and some cancers. The World Health Organization even states that more people die each year from the consequences of obesity than from hunger. Something must be done to stem the tsunami of obesity and its resultant medical complications. Our work and that of others suggests that new obesity treatments and anti-obesity medications should be based on those already successful in treating other addictions. This paper looks at empirical evidence linking addictions to food and to drugs such as tobacco, alcohol, cannabis, amphetamines, and cocaine. Hypotheses are put forth as to why hyperphagia is so difficult to treat. Additionally, prenatal programming for addiction is explored. Lessons from successful drug treatment are elucidated and potential pharmaceutical targets for hyperphagia and obesity are suggested.
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PMID:Drug withdrawal and hyperphagia: lessons from tobacco and other drugs. 2149 91

The senior patient and/or the geriatrician are confronted with a confusing literature describing how patients interested in combating metabolic syndrome, diabesity (diabetes plus obesity) or simple obesity might best proceed. The present paper gives a brief outline of the basic disease processes that underlie metabolic pro-inflammation, including how one might go about devising the most potent and practical detoxification from such metabolic compromise. The role that dietary restriction plays in pro-inflammatory detoxification (detox), including how a modified fast (selective food abstinence) is incorporated into this process, is developed. The unique aspects of geriatric bariatric medicine are elucidated, including the concepts of sarcopenia and the obesity paradox. Important caveats involving the senior seeking weight loss are offered. By the end of the paper, the reader will have a greater appreciation for the challenges and opportunities that lie ahead for geriatric patients who wish to overcome food addiction and reverse pro-inflammatory states of ill-heath. This includes the toxic metabolic processes that create obesity complicated by type 2 diabetes mellitus (T2DM) which collectively we call diabesity. In that regard, diabesity is often the central pathology that leads to the evolution of the metabolic syndrome. The paper also affords the reader a solid review of the neurometabolic processes that effectuate anorexigenic versus orexigenic inputs to obesity that drive food addiction. We argue that these processes lead to either weight gain or weight loss by a tripartite system involving metabolic, addictive and relational levels of organismal functioning. Recalibrating the way we negotiate these three levels of daily functioning often determines success or failure in terms of overcoming metabolic syndrome and food addiction.
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PMID:Food addiction: detox and abstinence reinterpreted? 2326 44

Cigarette smoking and alcohol use are prevalent among individuals with diabetes in the US, but little is known about screening and treatment for substance use disorders in the diabetic population. This commentary discusses the scope and clinical implications of the public health problem of coexisting substance use and diabetes, including suggestions for future research. Diabetes is the seventh leading cause of death in the US, and is associated with many severe health complications like cardiovascular disease, stroke, kidney damage, and limb amputations. There are an estimated 24 million adults in the US with type 2 diabetes. Approximately 20% of adults aged 18 years or older with diabetes report current cigarette smoking. The prevalence of current alcohol use in the diabetic population is estimated to be around 50%-60% in epidemiological surveys and treatment-seeking populations. Cigarette smoking is associated with an increased risk of type 2 diabetes in a dose-dependent manner and is an independent modifiable risk factor for development of type 2 diabetes. Diabetic patients with an alcohol or other drug use disorder show a higher rate of adverse health outcomes. For example, these patients experience more frequent and severe health complications as well as an increased risk of hospitalization, and require longer hospital stays. They are also less likely to seek routine care for diabetes or adhere to diabetes treatment than those without an alcohol or other drug use disorder. The Affordable Care Act of 2010 and the Mental Health Parity Act and Addiction Equity Act of 2008 provide opportunities for facilitating integration of preventive services and evidence-based treatments for substance use disorders with diabetes care in community-based medical settings. These laws also offer emerging areas for research.
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PMID:Integrating substance abuse care with community diabetes care: implications for research and clinical practice. 2337 92

Variants (such as rs9939609) in the fat mass- and obesity-associated (FTO) gene have been associated with obesity, type 2 diabetes, some cancers, and alcohol consumption. This study tested the associations of 167 single-nucleotide polymorphisms (SNPs) within FTO gene with alcohol dependence (AD) using two Caucasian samples: the Collaborative Study on the Genetics of Alcoholism (COGA) sample (660 AD cases and 400 controls) and the Study of Addiction: Genetics and Environment (SAGE) sample (623 cases and 1,016 controls). Logistic regression analysis of AD as a binary trait was performed using the PLINK software. For the SAGE sample, the top three SNPs showing associations with AD were rs8062891, rs1108086, and rs1420318 (p = 0.00088, 0.00086 and 0.00086, respectively). Two SNPs (rs12597786 and rs7204609) associated with AD in the SAGE sample (p = 0.017 and 0.034, respectively) were replicated in the COGA sample (p = 0.017 and 0.014, respectively). Through meta-analysis of two samples using PLINK, the top three SNPs associated with AD were rs8062891, rs12597786, and rs7204609 (p = 0.00064, 0.00076 and 0.0011, respectively). Haplotype analysis in the SAGE sample further supported the associations with AD in single-marker analysis. In addition, we found association of rs17817449 (which has a strong linkage disequilibrium with rs9939609) with AD in the SAGE sample (p = 0.00339). The findings provide evidence of joint intervention and prevention of AD and obesity.
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PMID:Genetic variants in the fat mass- and obesity-associated (FTO) gene are associated with alcohol dependence. 2377 86


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