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One of the earliest pointers to an autoimmune aetiology was the observation that other autoimmune conditions were over-represented in juvenile cases of diabetes and their relatives, but not in late-onset cases.
Autoantibodies directed against islet constituents precede the onset of clinical disease by many years and can be used to predict it; they are present in 95% of newly presenting patients. Several islet antigens have been characterised, and these include insulin itself, the enzyme glutamic acid decarboxylase (GAD), protein tyrosine phosphatase (IA-2) and the cation transporter ZnT8.
Autopsies of younger patients who died shortly after diagnosis of diabetes show variable degrees of lymphocytic infiltration, resembling that seen in autoimmune thyroiditis. Nerup observed in 1971 that leucocyte migration was inhibited by the presence of islet tissue in juvenile but not late-onset cases.
Although there have been occasional case reports of diabetes developing rapidly after fulminant viral infections, the typical long latent period suggests that diabetes is rarely the direct of consequence of direct damage by viral infection. Further evidence of autoimmunity in type 1 diabetes has accumulated over the past 25 years.
Evidence in humans is more anecdotal, and comes from bone marrow transplantation from donors with type 1 diabetes to non-diabetic recipients. Final proof that immune processes mediate human type 1 diabetes comes from trials of immune intervention. Infection of the pancreas by viruses triggers the activation and recruitment of innate immune cells such as macrophages, dendritic cells (DCs) and natural killer (NK) cells, which produce pro-inflammatory cytokines through cytoplasmic pattern recognition receptor (PRR) activation. A big credit to rising life expectancy trends goes to pharmaceutical companies for improved treatments options to many of these diseases and disorders. Harris, on behalf of the MetLife Foundation, conducted its survey in September 2010 by asking 1,007 U.S. Diabetes is often brushed aside as a nuisance rather than a serious disease, but prolonged exposure to high blood sugar can cause heart attack, stroke, and kidney failure. Just last week, actor Tom Hanks admitted that he has been dealing with symptoms of type 2 diabetes for the past two decades. To put heart disease's mortality into scope, the fourth through 10th leading causes of death in 2010 don't combine to account for the number of deaths caused by heart disease.
An exciting new treatment to watch here would be Pfizer and Merck's Liptruzet, which is targeted as an LDL-cholesterol lowering drug (the bad type of cholesterol).
Perhaps the biggest reason Alzheimer's jumps up the list is because it's one of the most misunderstood and relatively untreatable diseases still out there. The disease itself is incredibly tricky to treat because of the blood-brain barrier, which makes getting medication from the blood into the brain difficult.
When it comes to treating Alzheimer's, I would suggest keeping your eye on Eli Lilly despite its late-stage disappointment with solanezumab.
Two more cancer-focused biotechs that could change the gameThe best way to play the biotech space is to find companies that shun the status quo and instead discover revolutionary, groundbreaking technologies. Fool contributor Sean Williams has no material interest in any companies mentioned in this article. Acanthosis nigricans is an asymptomatic darkening and thickening of certain areas of the skin associated with insulin resistance.
Necrobiosis lipoidica dibeticorum (NLD) is a collagen degeneration disease that results in a granulomatous response, thickening of blood vessel walls & fat deposition.
Bullous diabeticorum is a distinct, spontaneous, noninflammatory blistering condition of acral skin that resembles burn blisters and occurs in 0.5% of patients with diabetes – usually among those with severe forms of the disease and neuropathy. Eruptive xanthomatosis occurs when triglyceride levels in the blood rise to extremely high levels due to severe insulin resistance.
Granuloma annulare is a benign self-limited dermatosis that has been epidemiologically linked to diabetes and necrobiosis lipoidica diabeticorum.
Vitiligo, an autoimmune disorder in which the destruction of melanocytes results in skin depigmentation, occurs at a higher incidence among adults with type 1 diabetes. Nearly one-third of patients with diabetes have some type of dermatologic manifestation and, with time, the skin of all patients with diabetes will be affected in some form or another. Type 1 diabetes overlaps with autoimmune thyroid disease, coeliac disease, Addison’s disease and pernicious anaemia among other organ-specific autoimmune conditions (see Figure 1).
Moreover, they are also more prevalent in first degree relatives of patients than in the general population (Figure 2). Cell transfer experiments in the NOD mouse have established that autoimmune diabetes is a T cell mediated disease requiring the presence of both CD4 and CD8 cells. Viruses do however show tissue tropism, mouse models of virally-induced diabetes are available, and the phenomenon of MHC-restriction (susceptibility to specific viruses associated with certain HLA types) is well established.
Unaffected monozygotic twins in long-term discordant pairs are considered unlikely to develop type 1 diabetes, and can therefore donate the tail of their pancreas to their affected co-twin. According to the World Health Organization's International Classification of Disease, version 10, there are 12,420 different types of diseases in the world.


Certain diagnoses have a way of inspiring fear in Americans unlike others, which is why, in 2011, Harris Interactive set out to discover exactly what those were.
Rather, they develop diabetes through some mixture of genetics and lifestyle habits such as poor food choices or lack of physical exercise (type 2 diabetes).
It's my personal hope that having a high-profile role model in place will give this disease the acclaim it needs to get high-risk people to eat healthier and exercise more. The reason SGLT2 inhibitors are so exciting is that they work in the kidneys to block glucose absorption, as opposed to previous generations of diabetes drugs that worked out of the pancreas and kidneys.
4: Stroke (8%) Stroke was the fourth-leading cause of death in 2010, but you'd hardly know it with just 8% of Americans saying they fear it the most. Other factors that increased your chance of a stroke included hereditary factors like ethnicity and age, as well as existing medical conditions like high blood pressure, high cholesterol, and of course, diabetes. This revolutionary blood thinner was approved by the Food and Drug Administration in late December to prevent stroke in patients with atrial fibrillation. Liptruzet -- which is an oral medication comprised of Pfizer's generic Lipitor and Merck's cholesterol absorption inhibitor Zetia -- demonstrated an LDL reduction of 53%-61% in trials compared to just 37%-54% for Lipitor alone and 20% for Zetia as a monotherapy. 2: Alzheimer's disease (31%) Please note the monstrously large jump between heart disease at No.
Harris Interactive's poll notes that 62% of those polled admitted to knowing "nothing" or only "very little" about Alzheimer's. In 2012, international scientists chose solanezumab -- which attaches to amyloid floating free in the brain before it attaches and become plague -- and LY2886721 -- which blocks a specific enzyme used to make amyloid -- (as well as a drug from Roche) for a long-term (three-year) Alzheimer's study out of 15 possible drugs.
2 leading cause of death behind heart disease likely tops the rankings because of how quickly the disease can strike and the suffering it can cause. This experimental therapy has received the breakthrough therapy designation from the FDA and was recently submitted as a new drug applicant based on some incredible mid-stage study results. In The Motley Fool's brand-new FREE report "2 Game-Changing Biotechs Revolutionizing the Way We Treat Cancer," find out about a new technology that big pharma is endorsing through partnerships, and the two companies that are set to profit from this emerging drug class. This is a place for our readers to discuss, debate, and learn more about the Foolish investing topic you read about above.
Now you can create a personalized watchlist and get immediate access to the personalized information you need to make successful investing decisions. Patients develop tan or brown velvety plaques, most commonly on the intertriginous areas of the axilla, groin and posterior neck. Lesions present as asymptomatic, shiny, red-brown patches that increase in size over months to years, becoming more yellow & atrophic.
These blisters typically occur on the fingers, hands, toes, feet, legs or forearms, and are painless and self-limiting. Eruptive xanthomas appear as firm, yellow, waxy pea-like bumps on the skin that are surrounded by itchy, red halos.
Lesions appear as sharply defined, ring or arc-shaped firm, nontender soft tissue nodules on the extremities, scalp or forehead. The association between the two disorders remains unclear, but researchers have suggested that type 1 diabetes and vitiligo may share a common autoimmune etiology.
The ischemic patient will present with disproportionately excruciating pain associated with a superficial ulcer, while the neuropathic patient is unaware of a large, deep ulcer.
Some, such as diabetic bullae and necrobiosis lipoidica diabeticorum, can alert clinicians to the diagnosis of diabetes; whereas others, such as eruptive xanthomas can reflect the status of a patient’s glucose and lipid metabolism. Some investigators therefore conceive of type 1 diabetes as an condition in which beta cells subject to viral infection are capable of provoking a secondary immune-mediated response resulting in diabetes. The Wistar-derived rat from the Bio Breeding Laboratories of Canada Ltd – the BB rat – was first described in 1976. Attempts to graft from one twin to another were, however, foiled by recrudescence of the type 1 disease process in the transplanted organ. Activated antigen-presenting cells can present either self antigen or viral antigens (in the case of molecular mimicry) to islet antigen-specific T cells.
Approximately 90% of the aforementioned diabetes cases in this country are of the type 2 designation. This relatively low percentage could have a lot to do with the risk factors for stroke being pretty well-defined. This doesn't make the prospect of having a stroke less scary, but it does help narrow down a person's risk potential dramatically. When pitted side-by-side against Warfarin, which has been a blood-thinning mainstay for two decades, it outperformed in numerous categories.
With a whopping 35.7% of this country considered obese -- and obesity coming with a higher risk of high blood pressure, high cholesterol, and diabetes -- the deck is stacked against a good percentage of the population. Furthermore, Liptruzet also boosted the production of HDL cholesterol, the good type of cholesterol.


Furthermore, the poll indicates that even though 44% of respondents noted knowing a family member or friend with Alzheimer’s, only 18% of people have developed a plan should they get Alzheimer's, with regard to long-term care options and financial planning.
It's far too early to guess whether these compounds will be successful, but you have to like Eli Lilly’s chances with two of its experimental drugs being chosen out of 15 hopefuls. This isn't to say that the aforementioned diseases aren't debilitating, but treatment for many cancer types can involve painful surgeries, radiation and chemotherapy that can lead to unpleasant side effects, and very low success and survival rates depending on the cancer type. Ibrutinib is designed to treat mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL), the most common form of leukemia in adults.
We Fools may not all hold the same opinions, but we all believe that considering a diverse range of insights makes us better investors.
Lesions show marked hyperkeratosis and papillomatosis with mild acanthosis and hyperpigmentation. Most lesions have a fairly well defined border, occur on the lower extremities & can ulcerate if subjected to trauma.
These lesions typically occur on the face and buttocks, as well as the backs of arms, legs and hands. Papules are 1-5 mm in diameter, flesh-colored or slightly pink and smooth rather than scaly. It is recommended that clinicians evaluate patients who experience late-onset vitiligo for diabetes.
As many as four-fifths of patients with diabetes experience peripheral neuropathy, and the majority of ulceration occurs as a consequence of the loss of protective sensations such as temperature and pain. 1,25(OH)2D3 stimulates innate immune responses by enhancing the chemotactic and phagocytotic responses of macrophages as well as the production of antimicrobial proteins such as cathelicidin. The concept of viral causation is thus consistent with an immune-mediated aetiology of diabetes, but this is by no means established beyond doubt.
These non-obese animals developed a spontaneous insulin-deficient, ketosis-prone form of diabetes associated with histological features of insulitis. Many other forms of immunotherapy have been tried since then, with (as yet) limited success. The pro-inflammatory milieu created by the innate immune cells promotes the recruitment and activation of islet antigen-specific T cells in the pancreas. In addition, previous type 2 diabetes medications either caused weight gain or were weight neutral as in the case of DPP-4 inhibitors, but Invokana was actually shown to induce weight loss in patients!
It's hard not to be concerned with heart disease because there are so many variables that act as risk factors, including high blood pressure, high cholesterol, obesity, diabetes, poor diet, your gender, and family history.
Some of the more common cancer types like lung cancer and pancreatic cancer carry with them five-year survival rates of just 17% and 6%, respectively. In MCL trials, ibrutinib delivered an overall response rate (ORR) of 68% with a median response duration of 17.5 months while offering an ORR of 71% in treating CLL. In 2000, the American Diabetes Association established acanthosis nigricans as a formal risk factor for diabetes in children. Eruptions generally resolve when glycemic control is restored, but lipid-lowering drugs may also be needed. Presence of various-auto-antibodies in patients with recent onset type 1 diabetes, in their first-degree relatives and in healthy controls.
The most widely-used model of type 1 diabetes, the non-obese diabetic (NOD) mouse, was described in 1980. Viral infection can be controlled by invariant NKT (iNKT) cell–plasmacytoid DC (pDC) crosstalk leading to a rapid elimination of the virus from the pancreas.
I'll also add some investing flair by noting an existing or upcoming drug worth keeping an eye on within each disease type that could have an opportunity to significantly change things for the better.
At the level of the APC (like the DC), 1,25(OH)2D3 inhibits the surface expression of MHC-II-complexed antigen and of co-stimulatory molecules, in addition to production of the cytokines IL-12 and IL-23, thereby indirectly shifting the polarization of T cells from a Th1 and Th17 phenotype towards a Th2 phenotype. In addition, 1,25(OH)2D3 directly affects T cell responses, by inhibiting the production of Th1 cytokines (IL-2 and IFN-γ) and Th17 cytokines (IL-17 and IL-21), and by stimulating Th2 cytokine production (IL-4).
The complex interplay between viruses and immune cells reflects the dual role, beneficial or detrimental, of infections in the development of type 1 diabetes. Moreover, 1,25(OH)2D3 favors Treg cell development via modulation of DCs and by directly targeting T cells.



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