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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Familial aggregation has been shown for type 1 diabetes (T1D) although the nature of the factors (environment and/or genetics) responsible remains unclear. Familial clustering of diabetic nephropathy as well as of increased cardiovascular morbidity and early mortality has also been observed. This review describes the nearly 20 years history of our investigation in parallel with contemporary literature. The story is presented from the early years' strong focus on possible markers of T1D nephropathy (urinary albumin, urinary enzymes, erythrocyte Na/Li countertransport, and erythrocyte Na/H exchange) to the last clinical investigations to determine relevant biological markers of familial predisposition to T1D. Our studies of case-families recruited unaffected first-degree relatives of sporadic T1D cases and population-based controls. Unlike multiple-case families, these families are those less likely to carry a strong genetic predisposition. Participants were both interviewed and provided biological material for a detailed functional characterisation of their biochemical phenotype. These studies have initially excluded that the erythrocyte Na/H exchange could be a marker of diabetic nephropathy. On the contrary, NHE activity was significantly higher in T1D family members independently of the presence of renal disease. Basic science knowledge of NHE and its functional implications have also been reviewed. Unexpectedly, we found evidence of increased oxidative stress in nondiabetic normotensive relatives of T1D patients, apart from soluble markers of autoimmunity and despite seemingly intact antioxidant defences. Markers of oxidation were associated with markers of inflammation and we concluded that the familial increase in NHE activity could be ascribed to the direct stimulatory effect of oxidative stress. Relatives showed also immunological hallmarks and cardiovascular abnormalities that were related to indices of oxidative stress and metabolic syndrome. Other peculiarities emerged from measuring the erythrocytes redox system that exports electrons across the cell membrane to external oxidants as a function of cytoplasmic electron donor concentration. This electron transfer might reflect the functional state of membrane proton pumps that modulate intracellular redox levels. The transport system contributed to oxidation in T1D families, whereas in healthy people it protected from oxidation. Furthermore, dietary intake of vitamin C and sporting activities modulated erythrocyte electron transfer efficiency. The contribution of environmental factors was investigated using the European Prospective Investigation of Cancer and Nutrition questionnaires that provided evidence of common unhealthy dietary behaviours, which could even predispose to the development of diabetes and cardiovascular complications, in subjects living in Pisa. However, lifestyle of T1D relatives was indistinguishable from those of controls, except for the higher daily intake of niacin and the lower physical activity levels. No difference in smoking or alcohol consumption emerged among families and controls. The oxidative stress is a non-specific though certain component of pathogenesis at numerous diseases states of aerobic organisms. Although molecular genetic analysis has produced significant progress in T1D phenotype, much remains to be learned about the molecular sequence of events leading from a generic familial pro-oxidant background to a sporadic form of T1D (where oxidative damage targets the insulin-secreting cells).
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PMID:Building a bridge between clinical and basic research: the phenotypic elements of familial predisposition to type 1 diabetes. 1734 47

Membrane type-1 matrix metalloproteinase (MT1-MMP) shedding of the signaling and adhesion CD44 receptor plays a significant role in stimulating cancer cells locomotion. Similarly, and unexpectedly, MT1-MMP-dependent shedding of CD44 plays an equally significant role in regulating the adhesion to the pancreatic vasculature and also in the concomitant transendothelial migration and intra-islet homing of the diabetogenic, cytotoxic, T cells. Inactivation of the T cell MT1-MMP functionality by clinically tested, synthetic inhibitors leads to an extended immobilization of the T killer cells on the pancreatic vasculature and, subsequently, to immunosuppression because of the cessation of the T cell transmigration and homing. Injections of insulin jointly with an MT1-MMP inhibitor stimulated the regeneration of functional, insulin-producing, beta-cells in acutely diseased non-obese diabetic (NOD) mice. After insulin injections were suspended and inhibitor injections continued, diabetic NOD mice maintained mild hyperglycemia and did not require further insulin injections for survival. Overall, these data provide a substantive mechanistic rationale for clinical trials of the inhibitors of MT1-MMP in human type 1 diabetes.
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PMID:Defining the roles of T cell membrane proteinase and CD44 in type 1 diabetes. 1736 74

A shared and additive genetic variance component-long-term survivor (LTS) model for familial aggregation studies of complex diseases with variable age-at-onset phenotype and non-susceptible subjects in the study cohort is proposed. LTS has been used from the early 1970s, especially in epidemiological studies of cancer. The LTS model utilizes information on the age at onset (survival) distribution to make inference on partially latent susceptibility. Bayesian modeling with uninformative priors is used and estimates of the posterior distribution of age at onset and susceptibility parameters of interest have been obtained using Bayesian Markov chain Monte Carlo (MCMC) methods with OpenBugs program. A simulation study confirms that we obtain posterior estimates of the model parameters on shared and genetic variance components of age at onset and susceptibility with good coverage rates. Further, we analyze familial aggregation of diabetic nephropathy (DN) in large Finnish cohort of 528 sibships with type 1 diabetes (T1D). According to the variance components estimated a substantial familial variation in the susceptibility to DN exist among families, while time to DN is less influenced by shared familial factors.
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PMID:Genetic random effects model for family data with long-term survivors: analysis of diabetic nephropathy in type 1 diabetes. 1748 84

The immune system has evolved to protect the host from microbial infection; nevertheless, a breakdown in the immune system often results in infection, cancer, and autoimmune diseases. Multiple sclerosis, rheumatoid arthritis, type 1 diabetes, inflammatory bowel disease, myocarditis, thyroiditis, uveitis, systemic lupus erythromatosis, and myasthenia gravis are organ-specific autoimmune diseases that afflict more than 5% of the population worldwide. Although the etiology is not known and a cure is still wanting, the use of herbal and dietary supplements is on the rise in patients with autoimmune diseases, mainly because they are effective, inexpensive, and relatively safe. Curcumin is a polyphenolic compound isolated from the rhizome of the plant Curcuma longa that has traditionally been used for pain and wound-healing. Recent studies have shown that curcumin ameliorates multiple sclerosis, rheumatoid arthritis, psoriasis, and inflammatory bowel disease in human or animal models. Curcumin inhibits these autoimmune diseases by regulating inflammatory cytokines such as IL-1beta, IL-6, IL-12, TNF-alpha and IFN-gamma and associated JAK-STAT, AP-1, and NF-kappaB signaling pathways in immune cells. Although the beneficial effects of nutraceuticals are traditionally achieved through dietary consumption at low levels for long periods of time, the use of purified active compounds such as curcumin at higher doses for therapeutic purposes needs extreme caution. A precise understanding of effective dose, safe regiment, and mechanism of action is required for the use of curcumin in the treatment of human autoimmune diseases.
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PMID:Curcumin and autoimmune disease. 1756 23

Breastfeeding plays a key role in the programming process during early life but, due to confounding factors, it is difficult to draw conclusions on long-term health benefits. The magnitude of the beneficial effect of breastfeeding on blood pressure (-2 mmHg) and total cholesterol (-0.2 mmol/l) is likely to have public health implications. However, it is unknot known whether breastfeeding reduces the risk of cardiovascular mortality. Breastfeeding may protect against the development of celiac disease. The protective role of breastfeeding against type 1 diabetes seems likely, but the mechanisms involved are still under discussion. There is no convincing evidence that breastfeeding reduces the risk of leukemia and cancer. Breastfeeding is associated with a better cognitive development (-3 points) that is present as early as at 6 months of age and sustained throughout childhood and adolescence. The benefits of breast milk may be related to its high content in docosahexaenoic acid which plays an important role in brain development. Increasing the duration of breastfeeding is correlated with an increase in cognitive development.
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PMID:Later effects of breastfeeding practice: the evidence. 1766 95

We report a case of diabetic mastopathy in an elderly woman with type 2 diabetes. The patient was a 69-year-old woman diagnosed with type 2 diabetes at the age of 33 years. She had been treated with insulin for 25 years, however, her blood glucose had been poorly controlled. She noticed bilateral breast lumps in September 2002. Mammography of the breast showed increased density in the glandular pattern and architectural distortion without focal mass and microcalcification. Ultrasonography of the breast showed an irregular-shaped hypoechoic mass with an acoustic shadow. As malignancy needed to be excluded, core needle biopsy was performed in the left breast and diabetic mastopathy was confirmed pathologically. Diabetic mastopathy is usually a complication of pre-menopausal type 1 diabetes and develops in a unilateral breast. This case developed in bilateral breasts in an elderly type 2 diabetic patient.
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PMID:Diabetic mastopathy of bilateral breasts in an elderly Japanese woman with type 2 diabetes: a case report and a review of the literature in Japan. 1787 45

Individuals are capable of producing vitamin D with proper exposure to sunlight. However, several factors can interfere with the effectiveness of this process. Most sunscreens filter out UVB light, thus inhibiting vitamin D production. Individuals with more darkly pigmented skin have greater difficulty producing vitamin D because melanin acts as an effective natural sunscreen, requiring longer sun exposure to produce an adequate daily allotment of vitamin D. Additionally, solely breastfed infants whose mothers suffered from vitamin D deficiency or insufficiency when pregnant have smaller reserves of the nutrient and are at greater risk of developing nutritional rickets. Vitamin D deficiency leads to rickets, osteomalacia, and osteoporosis. Long-term vitamin D insufficiency can lead to paracrine effects such as type 1 diabetes, cancer, and multiple sclerosis. This article reviews the current literature on vitamin D deficiency and insufficiency and their relation to different disease states. Potential areas for research are discussed.
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PMID:The effects of vitamin D deficiency and insufficiency on the endocrine and paracrine systems. 1790 64

Celiac disease (CD) or gluten sensitive enteropathy is relatively common in western populations with prevalence around 1%. With the recent availability of sensitive and specific serological testing, many patients who are either asymptomatic or have subtle symptoms can be shown to have CD. Patients with CD have modest increases in risks of malignancy and mortality compared to controls. The mortality among CD patients who comply poorly with a gluten-free diet is greater than in compliant patients. The pattern of presentation of CD has altered over the past three decades. Many cases are now detected in adulthood during investigation of problems as diverse as anemia, osteoporosis, autoimmune disorders, unexplained neurological syndromes, infertility and chronic hypertransaminasemia of uncertain cause. Among autoimmune disorders, increased prevalence of CD has been found in patients with autoimmune thyroid disease, type 1 diabetes mellitus, autoimmune liver diseases and inflammatory bowel disease. Prevalence of CD was noted to be 1% to 19% in patients with type 1 diabetes mellitus, 2% to 5% in autoimmune thyroid disorders and 3% to 7% in primary biliary cirrhosis in prospective studies. Conversely, there is also an increased prevalence of immune based disorders among patients with CD. The pathogenesis of co-existent autoimmune thyroid disease and CD is not known, but these conditions share similar HLA haplotypes and are associated with the gene encoding cytotoxic T-lymphocyte-associated antigen-4. Screening high risk patients for CD, such as those with autoimmune diseases, is a reasonable strategy given the increased prevalence. Treatment of CD with a gluten-free diet should reduce the recognized complications of this disease and provide benefits in both general health and perhaps life expectancy. It also improves glycemic control in patients with type 1 diabetes mellitus and enhances the absorption of medications for associated hypothyroidism and osteoporosis. It probably does not change the natural history of associated autoimmune disorders.
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PMID:Celiac disease and autoimmune thyroid disease. 1805 28

Many viral infections reach clinical significance in winter, when it is cold, relative humidity is lowest and vitamin D production from solar ultraviolet-B irradiation is at its nadir. Several autoimmune diseases, such as multiple sclerosis, type 1 diabetes mellitus and asthma, are linked to viral infections. Vitamin D, through induction of cathelicidin, which effectively combats both bacterial and viral infections, may reduce the risk of several autoimmune diseases and cancers by reducing the development of viral infections. Some types of cancer are also linked to viral infections. The cancers with seemingly important risk from viral infections important in winter, based on correlations with increasing latitude in the United States, an index of wintertime solar ultraviolet-B dose and vitamin D, are bladder, prostate, testicular and thyroid cancer, Hodgkin's and non-Hodgkin's lymphoma, and, perhaps, gastric cancer. The evidence examined includes the role of viruses in the etiology of these diseases, the geographic and seasonal variation of these diseases, and the time of life when vitamin D is effective in reducing the risk of disease. In general, the evidence supports the hypothesis. However, further work is required to evaluate this hypothesis.
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PMID:Hypothesis--ultraviolet-B irradiance and vitamin D reduce the risk of viral infections and thus their sequelae, including autoimmune diseases and some cancers. 1843 23

Neoplasia was established in 5.4% out of 15,813 patients with diabetes mellitus registered at the City Population-Based Cancer Register and Territorial Diabetic Center, St. Petersburg. Gender-unrelated decreasing order of tumor sites was as follows: breast, skin, uterus, colon and stomach. Broncho-pulmonary and gastric cancer incidence in male patients with diabetes was higher than in females (3.5 and 2.2 times, respectively). The relationship was reversed with thyroid cancer and skin melanoma (4.4 and 2.3 times, respectively). In patients with type 1 diabetes mellitus (10.3%), the cancer incidence pattern differed significantly from that in the whole diabetes-associated cohort of cancer patients: the former tended to involve such sites as pancreas, urinary bladder, stomach, cervix uteri, lung and skin. Data on age at diagnosis of cancer or diabetes, insulin therapy intensity and body mass were evaluated. The value of timely screening for both cancer and diabetes mellitus in such cohorts was confirmed.
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PMID:[Registry-based analysis of cancer and diabetes combination: prevalence and features]. 1819 8


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