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)

Women suffer more often from depression than males, indicating that hormones might be involved in the etiology of this disease. Low as well as high testosterone (T) levels are related to depression and well-being in women, T plasma levels correlate to depression in a parabolic curve: at about 0.4-0.6 ng/ml plasma free T a minimum of depression is detected. Lower levels are related to depression, osteoporosis, declining libido, dyspareunia and an increase in total body fat mass. Androgen levels in women decrease continuously to about 50% before menopause compared to a 20-year-old women. Androgen levels even decline 70% within 24 h when women undergo surgical removal of the ovaries. Conventional oral contraception or HRT cause a decline in androgens because of higher levels of SHBG. Hyperandrogenic states exist, like hirsutism, acne and polycystic ovary syndrome. Social research suggests high androgen levels cause aggressive behavior in men and women and as a consequence may cause depression. Higher androgen values are more pronounced at young ages and before and after delivery of a baby and might be responsible for the "baby blues". It was found that depression in pubertal girls correlated best with an increase in T levels in contrast to the common belief that "environmental factors" during the time of growing up might be responsible for emotional "up and downs". T replacement therapy might be useful in perimenopausal women suffering from hip obesity, also named gynoid obesity. Abdominal obesity in men and women is linked to type 2 diabetes and coronary heart diseases. Testosterone replacement therapy in hypoandrogenic postmenopausal women might not only protect against obesity but also reduce the risk of developing these diseases. Antiandrogenic progestins might be useful for women suffering from hyperandrogenic state in peri- and postmenopause. Individual dosing schemes balancing side effects and beneficial effects are absolutely necessary. Substantial interindividual variability in T plasma values exists, making it difficult to utilize them for diagnostic purposes. Therefore a "four-level-hormone classification scheme" was developed identifying when estradiol (E) and T levels are out of balance. (1) Low E-low T levels are correlated with osteoporosis, depression, and obesity; (2) high E-low T with obesity, decreased libido; (3) high T-low E levels with aggression, depression, increased libido, and substance abuse; (4) high E-high T with type II diabetes risk, breast cancer and cardiovascular risk. Testosterone delivery systems are needed where beneficial and negative effects can be balanced. Any woman diagnosed for osteoporosis should be questioned for symptoms of depression.
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PMID:The impact of testosterone imbalance on depression and women's health. 1195 93

Diabetes mellitus affects approximately 135 million people in the world. Diabetes and hypertension are both relatively common diseases in westernised countries. Both entities increase with age. Essential hypertension accounts for the majority of hypertension in people with type 2 diabetes, who constitute more than 90% of those with a dual diagnosis of diabetes and hypertension. The benefit conferred per mm Hg blood pressure reduction appears to be greater in persons with type 2 diabetes than in those with hypertension and non-coexistent diabetes mellitus. Similar to a subset of patients with essential hypertension, type 2 diabetic patients manifest dietary NaCl-induced exacerbation of hypertension. Recent guidelines have emphasised that the target blood pressure levels for patients with diabetes should be lower than in other hypertensive groups. An increased total body sodium and enhanced vascular reactivity are found in people with diabetes and most type 2 diabetic patients are salt sensitive. Type 2 diabetes with hypertension is associated with reduced renal plasma flow when dietary salt intake is high. Experimental, observational and interventional evidence support the benefits of sodium restriction in hypertensives. However, the full effects of sodium restriction are usually not obvious for at least 5 weeks. Other favourable effects of moderate reduction in sodium intake are a regress left ventricular hypertrophy, decrease in diuretic-induced potassium wastage, reduction in proteinuria, protection against stroke and from osteoporosis and renal stones, and enhancement of the antihypertensive effect of the antihypertensive agents.
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PMID:Salt intake, hypertension and diabetes mellitus. 1198 94

The RecQ family of DNA helicases have potential roles in DNA repair, replication and/or recombination pathways. In humans, a defect in the RecQ family helicases encoded by the BLM, WRN and RECQ4 genes gives rise to Bloom's (BS), Werner's (WS) and Rothmund-Thomson (RTS) syndromes, respectively. These disorders are associated with cancer predisposition and/or premature aging. In Bloom's syndrome, affected individuals are predisposed to many types of cancer at an early age. Werner's syndrome is a premature aging disorder with a complex phenotype, which includes many age-related disorders that develop from puberty, including greying and thinning of the hair, bilateral cataract formation, type II diabetes mellitus, osteoporosis and atherosclerosis. The phenotype of Rothmund-Thomson syndrome patients also consists of some features associated with premature aging, as well as predispositon to certain cancers. Here, we discuss the molecular basis of these RecQ helicase-deficient disorders.
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PMID:Premature aging in RecQ helicase-deficient human syndromes. 1220 42

The IGF system is important in regulation of fetal and childhood growth. In later life, IGF-I and IGF-binding protein-1 (IGFBP-1) have been implicated in the pathogenesis of arteriosclerosis. They are, thus, potential candidates in explaining the link between early growth and adult cardiovascular disease. We measured fasting serum IGF-I and IGFBP-1 concentrations in 394 men and women from a cohort of 7086 individuals, born between 1924 and 1933 in Helsinki, Finland, whose weight and height were recorded at birth and from 7 to 15 yr of age. They also underwent clinical examination, including measurement of body fat using bioimpedance, blood pressure, glucose tolerance, and plasma insulin and fibrinogen concentrations. Serum IGF-I was positively correlated with fasting glucose (r = 0.10, P = 0.06) and fibrinogen (r = 0.19, P = 0.0001) concentrations and blood pressure (systolic and diastolic r = 0.10, P </= 0.05) and inversely with percentage body fat (r = -0.13, P = 0.01) and waist circumference (r = -0.11, P = 0.03). IGFBP-1 was inversely correlated with adult body mass index (BMI) (r = -0.46, P < 0.0001), fasting glucose and insulin concentrations, and blood pressure. There were correlations between the adult level of IGFBP-1 and birth weight (r = 0.11, P = 0.03) and ponderal index (weight/length(3)) at birth (r = 0.13, P = 0.01), but IGF-I was not related to birth measurements. There were interactive effects between childhood height or BMI and adult BMI on IGF-I and IGFBP-1 in adulthood. Tall height and high BMI at 7 yr were associated with low IGF-I (P = 0.03 for height and P = 0.003 for BMI) and high IGFBP-1 (P = 0.02 and P = 0.06) in adulthood but only in those subjects whose current BMI was below median. On further analysis these interactive effects were particularly strong for height in childhood and adult lean BMI (lean body mass/height(2)). Among men and women of below-average lean BMI, tall height at 7 yr was associated with low adult IGF-I (P = 0.007) and high IGFBP-1 (P = 0.0004) concentrations [interaction (7-yr height x adult lean BMI); P = 0.008 for IGF-I and 0.001 for IGFBP-1]. There is no evidence that reduced fetal growth programs IGF-I concentrations in old age. An association between small size at birth and low IGFBP-1 concentrations may in part reflect fetal programming effects on insulin resistance. Given the anabolic effects of the GH-IGF-I axis, subjects with tall height in childhood but low adult lean body mass may be at risk of late-life GH-IGF-I axis dysfunction. Prospective studies should address whether this group is susceptible to type 2 diabetes, coronary heart disease, and osteoporosis.
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PMID:Serum insulin-like growth factor (IGF)-I and IGF-binding protein-1 in elderly people: relationships with cardiovascular risk factors, body composition, size at birth, and childhood growth. 1262 86

Osteoporosis is the most prevalent metabolic bone disease in the United States. Although the disease has historically been reported mostly in white women, it can affect individuals of both sexes and all ethnic groups. The presence of osteoporosis related to diabetes is not well acknowledged and the impact of osteoporosis in a diabetic patient is often not considered. Routine screening or initiation of preventive medications for osteoporosis in all patients with type 1 or type 2 diabetes is not recommended at the present time. However, in all patients with diabetes, besides optimal glycemic control, general recommendations regarding adequate dietary calcium intake, regular exercise, and avoidance of other potential risk factors such as smoking should be given. In patients who have positive risk factors for osteoporosis, or in those who present with fractures, evaluation of bone density should be done and respective preventive or therapeutic interventions should be applied.
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PMID:Osteoporosis and diabetes. 1264 44

This cross-sectional cohort study of 5566 women and 2187 men 50 years of age and older in the population-based Canadian Multicentre Osteoporosis Study was conducted to determine whether reported past diseases are associated with bone mineral density or prevalent vertebral deformities. We examined 12 self-reported disease conditions including diabetes mellitus (types 1 or 2), nephrolithiasis, hypertension, heart attack, rheumatoid arthritis, thyroid disease, breast cancer, inflammatory bowel disease, neuromuscular disease, Paget's disease, and chronic obstructive pulmonary disease. Multivariate linear and logistic regression analyses were performed to determine whether there were associations among these disease conditions and bone mineral density of the lumbar spine, femoral neck, and trochanter, as well as prevalent vertebral deformities. Bone mineral density measurements were higher in women and men with type 2 diabetes compared with those without after appropriate adjustments. The differences were most notable at the lumbar spine (+0.053 g/cm2), femoral neck (+0.028 g/cm2), and trochanter (+0.025 g/cm2) in women, and at the femoral neck (+0.025 g/cm2) in men. Hypertension was also associated with higher bone mineral density measurements for both women and men. The differences were most pronounced at the lumbar spine (+0.022 g/cm2) and femoral neck (+0.007 g/cm2) in women and at the lumbar spine (+0.028 g/cm2) in men. Although results were statistically inconclusive, men reporting versus not reporting past nephrolithiasis appeared to have clinically relevant lower bone mineral density values. Bone mineral density differences were -0.022, -0.015, and -0.016 g/cm2 at the lumbar spine, femoral neck, and trochanter, respectively. Disease conditions were not strongly associated with vertebral deformities. In summary, these cross-sectional population-based data show that type 2 diabetes and hypertension are associated with higher bone mineral density in women and men, and nephrolithiasis may be associated with lower bone mineral density in men. The importance of these associations for osteoporosis case finding and management require further and prospective studies.
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PMID:Associations among disease conditions, bone mineral density, and prevalent vertebral deformities in men and women 50 years of age and older: cross-sectional results from the Canadian Multicentre Osteoporosis Study. 1267 40

Shifting dietary patterns, a decline in energy expenditure associated with a sedentary lifestyle, an ageing population--together with tobacco use and alcohol consumption--are major risk factors for noncommunicable diseases and pose an increasing challenge to public health. This report of a Joint WHO/FAO Expert Consultation reviews the evidence on the effects of diet and nutrition on chronic diseases and makes recommendations for public health policies and strategies that encompass societal, behavioural and ecological dimensions. Although the primary aim of the Consultation was to set targets related to diet and nutrition, the importance of physical activity was also emphasized. The Consultation considered diet in the context of the macro-economic implications of public health recommendations on agriculture and the global supply and demand for fresh and processed foodstuffs. In setting out ways to decrease the burden of chronic diseases such as obesity, type 2 diabetes, cardiovascular diseases (including hypertension and stroke), cancer, dental diseases and osteoporosis, this report proposes that nutrition should be placed at the forefront of public health policies and programmes. This report will be of interest to policy-makers and public health professionals alike, in a wide range of disciplines including nutrition, general medicine and gerontology. It shows how, at the population level, diet and exercise throughout the life course can reduce the threat of a global epidemic of chronic diseases.
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PMID:Diet, nutrition and the prevention of chronic diseases. 1276 90

Overproduction of IL-6, a proinflammatory cytokine, is associated with a spectrum of age-related conditions including cardiovascular disease, osteoporosis, arthritis, type 2 diabetes, certain cancers, periodontal disease, frailty, and functional decline. To describe the pattern of change in IL-6 over 6 years among older adults undergoing a chronic stressor, this longitudinal community study assessed the relationship between chronic stress and IL-6 production in 119 men and women who were caregiving for a spouse with dementia and 106 noncaregivers, with a mean age at study entry of 70.58 (SD = 8.03) for the full sample. On entry into this portion of the longitudinal study, 28 of the caregivers' spouses had already died, and an additional 50 of the 119 spouses died during the 6 years of this study. Levels of IL-6 and health behaviors associated with IL-6 were measured across 6 years. Caregivers' average rate of increase in IL-6 was about four times as large as that of noncaregivers. Moreover, the mean annual changes in IL-6 among former caregivers did not differ from that of current caregivers even several years after the death of the impaired spouse. There were no systematic group differences in chronic health problems, medications, or health-relevant behaviors that might have accounted for caregivers' steeper IL-6 slope. These data provide evidence of a key mechanism through which chronic stressors may accelerate risk of a host of age-related diseases by prematurely aging the immune response.
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PMID:Chronic stress and age-related increases in the proinflammatory cytokine IL-6. 1284 Jan 46

Variation in the circulating concentrations of the insulin-like growth factor (IGF) system has been implicated in the etiology of chronic diseases including cancer (prostate, breast, colon, and lung), heart disease, type 2 diabetes, and osteoporosis. We searched for sociodemographic, anthropometric, reproductive, lifestyle, and dietary determinants of IGF-I and insulin-like growth factor binding protein (IGFBP) -3 serum concentrations. Serum samples were collected in a Singapore Chinese cohort with a mean age of 61 years. Subject information was assessed during an in-person interview. Radioimmunometrically measured IGF-I and IGFBP-3 concentrations were available for 312 men and 326 postmenopausal women ages 50 years or older. Mean IGF-I concentrations were 144 ng/ml and 121 ng/ml for men and women, respectively (gender difference, P < 0.0001), and mean IGFBP-3 concentrations were 3710 ng/ml and 4147 ng/ml for men and women, respectively (gender difference, P < 0.0001). IGF-I and IGFBP-3 decreased with age (P for trend <0.0001); the age-related decrease in the IGF-I:IGFBP-3 molar ratio was stronger in women than men. IGF-I concentrations were higher among physically inactive subjects and among women with an early age at menarche. Consumption of saturated fat was found to decrease, and intake of omega-3 polyunsaturated fatty acids and of dietary fiber was found to increase circulating IGFBP-3 concentrations. Intake of calcium from food and supplement was associated positively with circulating IGF-I, IGFBP-3, and molar ratio. Intake of soy was associated positively with IGF-I and molar ratio concentrations, but only in men. The results of this study lend additional support to the hypothesis that circulating IGF-I concentrations increase the risk of prostate, bladder, colorectal, and breast cancer.
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PMID:Determinants of circulating insulin-like growth factor I and insulin-like growth factor binding protein 3 concentrations in a cohort of Singapore men and women. 1291 5

Somatomedin-1 binding protein-3 [insulin-like growth factor-1 binding protein-3, SomatoKine] is a recombinant complex of insulin-like growth factor-1 (rhIGF-1) and binding protein-3 (IGFBP-3), which is the major circulating somatomedin (insulin-like growth factor) binding protein; binding protein-3 regulates the delivery of somatomedin-1 to target tissues. Somatomedin-1 binding protein-3 has potential as replacement therapy for somatomedin-1 which may become depleted in indications such as major surgery, organ damage/failure and traumatic injury, resulting in catabolism. It also has potential for the treatment of osteoporosis; diseases associated with protein wasting including chronic renal failure, cachexia and severe trauma; and to attenuate cardiac dysfunction in a variety of disease states, including after severe burn trauma. Combined therapy with somatomedin-1 and somatomedin-1 binding protein-3 would prolong the duration of action of somatomedin-1 and would reduce or eliminate some of the undesirable effects associated with somatomedin-1 monotherapy. Somatomedin-1 is usually linked to binding protein-3 in the normal state of the body, and particular proteases clip them apart in response to stresses and release somatomedin-1 as needed. Therefore, somatomedin-1 binding protein-3 is a self-dosing system and SomatoKine would augment the natural supply of these linked compounds. Somatomedin-1 binding protein-3 was developed by Celtrix using its proprietary recombinant protein production technology. Subsequently, Celtrix was acquired by Insmed Pharmaceuticals on June 1 2000. Insmed and Avecia, UK, have signed an agreement for the manufacturing of SomatoKine and its components, IGF-1 and binding protein-3. CGMP clinical production of SomatoKine and its components will be done in Avecia's Advanced Biologics Centre, Billingham, UK, which manufactures recombinant-based medicines and vaccines with a capacity of up to 1000 litres. In 2003, manufacturing of SomatoKine is planned to move to Avecia's larger facility with a capacity of 10 000 litres. Somatomedin-1 binding protein-3 was originally licenced to Welfide for Japan. On October 1 2001, Welfide Corporation merged with Mitsubishi-Tokyo Pharmaceuticals to form Mitsubishi Pharma Corporation. The new company is a subsidiary of Mitsubishi Chemical. In April 2003 Insmed initiated a named patient programme in Europe, that will make available somatomedin-1 binding protein-3 for the treatment of growth hormone insensitivity syndrome (GHIS)--Laron syndrome. The treatment of patients was initiated in Scandinavia, with authorisation pending in several other European countries. Somatomedin-1 binding protein-3 will be made available to those GHIS patients who, in the opinion of their doctor, may benefit from IGF-1 therapy. At precommercial scale quantities, the drug will be available on a limited basis. Safety data generated from the named patient programme will be used to support marketing applications in 2004. A phase II dose-ranging study in children with GHIS was completed at Saint Bartholomew's and the Royal London School of Medicine, London, UK. A single dose of somatomedin-1 binding protein-3 delivered the same amount of IGF-1 as two daily injections of unbound IGF-1. There were no adverse events reported. GHIS is a genetic condition in which patients do not produce adequate quantities of IGF because of a failure to respond to the growth hormone signal. This results in a slower growth rate and short stature. Insmed has acquired an exclusive licence to Pharmacia's regulatory filings concerning yeast-derived IGF-1. These filings were used by Pharmacia to receive marketing approvals in several European countries and also in the investigational New Drug Application with the US FDA. This licence will facilitate the development of SomatoKine for the treatment of children with GHIS. In January 2003, Insmed announced positive results from a double-blind, placebo-controlled, dose-ranging study of SomatoKine in adolescent patients with type 1 diabetes mellitus redolescent patients with type 1 diabetes mellitus receiving insulin therapy. The study was conducted at the University of Cambridge, Cambridge, UK, under the supervision of Professor D. Dunger. It has also been granted orphan drug status for the treatment of GHIS--Laron syndrome in the US and in Europe. Celtrix has been granted 11 US patents for its recombinant protein production technology, which it used for developing somatomedin-1 binding protein-3. Subsequently, Celtrix was acquired by Insmed Pharmaceuticals on June 1 2000. Following the acquisition, Insmed announced that it intends to maintain the US rights to Celtrix's products portfolio. These US patents will expire between 2010 through 2017. Insmed is holding a US patent (expires in 2019) for the use of SomatoKine in the treatment of both type 1 and type 2 diabetes mellitus.
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PMID:Somatomedin-1 binding protein-3: insulin-like growth factor-1 binding protein-3, insulin-like growth factor-1 carrier protein. 1449 68


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