20^th Asia Pacific Diabetes Conference July 16-17, 2018 London ,UK

Several gene mutations have been linked to the development of type 2 diabetes. These gene mutations can interact with the environment and each other to further increase your risk. Type 2 diabetes is caused by both genetic and environmental factors.
Scientists have linked several gene mutations to a higher diabetes risk. Not everyone who carries a mutation will get diabetes. But many people with diabetes do have one or more of these mutations.
It can be difficult to separate genetic risk from environmental risk. The latter is often influenced by your family members. For example, parents with healthy eating habits are likely to pass them on to the next generation. On the other hand, genetics plays a big part in determining weight.
Mutations in any gene involved in controlling glucose levels can increase your risk of type 2 diabetes. These include genes that control:

·         production of glucose

·         production and regulation of insulin

·         how glucose levels are sensed in the body

Genes associated with type 2 diabetes risk include:

·         TCF7L2, which affects insulin secretion and glucose production

·         ABCC8, which helps regulate insulin

·         CAPN10, which is associated with type 2 diabetes risk in Mexican-Americans

·         GLUT2, which helps move glucose into the pancreas

·         GCGR, a glucagon hormone involved in glucose regulation

Metabolic syndrome is a cluster of conditions — increased blood pressure, high blood sugar, excess body fat around the waist, and abnormal cholesterol or triglyceride levels — that occur together, increasing your risk of heart disease, stroke and diabetes. Metabolic syndrome is closely linked to overweight or obesity and inactivity.
It's also linked to a condition called insulin resistance. Normally, your digestive system breaks down the foods you eat into sugar (glucose). Insulin is a hormone made by your pancreas that helps sugar enter your cells to be used as fuel.
In people with insulin resistance, cells don't respond normally to insulin, and glucose can't enter the cells as easily. As a result, glucose levels in your blood rise despite your body's attempt to control the glucose by churning out more and more insulin.

There are new findings regarding the comorbidity associated with rheumatic diseases. Both psoriasis and psoriatic arthritis have been found to be associated with metabolic syndrome. Recent research indicates prolonged chronic stress can contribute to metabolic syndrome by disrupting the hormonal balance of the hypothalamic-pituitary-adrenal axis (HPA-axis).

Endocrinology can be defined as a branch of biology that mainly deals with the study of endocrine system and related functions, secretions and diseases. Endocrine contains various glands. Every gland has its own secretion, known as hormone that performs specific functions.
Clinical endocrinology is a branch of medical sciences that involves the diagnosis, cure, prevention and treatment of irregular secretion and modified action of hormones. Molecular endocrinology, basically deals with the study of various functions of hormones secreted by different glands, at molecular level.
Molecular and Cellular Endocrinology focuses on molecular and cellular mechanisms in endocrinology by including: gene regulation, cell biology, signaling, mutations, transgenics, hormone-dependant cancers, nuclear receptors. Basic and pathophysiological studies at the molecule and cell level are considered.
 

Endocrine disorders  are often quite complex, involving a mixed picture of hyposecretion and hypersecretion because of the feedback mechanisms involved in the endocrine system. For example, most forms of hyperthyroidism are associated with an excess of thyroid hormone and a low level of thyroid stimulating hormone. Patients with multi-transfused thalassemia major may develop severe endocrine complications due to iron overload. The anterior pituitary is particularly sensitive to iron overload which disrupts hormonal secretion resulting in hypogonadism, short stature , acquired hypothyroidism and hypoparathyroidism. Glucose intolerance and diabetes mellitus are also common in thalassaemic patients. Delayed or absent puberty and hypogonadism may result in fertility problems which affect enormously the life of thalassemics. Glucose intolerance in adolescence and diabetes mellitus later in life are also frequent complications mainly due to iron overload, chronic liver disease and genetic predisposition. Primary hypothyroidism and hypoparathyroidsm usually appear in the second decade of life; are related to iron overload and may be reversible at an early stage by intensive chelation. Osteopenia and osteoporosis due to a complicated pathogenesis represent prominent causes of morbidity in young adults of both genders with thalassaemia. Early recognition and prevention of the endocrine complications, by early and regular chelation therapy, is mandatory for the improvement of the quality of life and psychological outcome of these patients.

Insulin is a hormone made by the pancreas that allows your body to use sugar (glucose) from carbohydrates in the food that you eat for energy or to store glucose for future use. Insulin helps keeps your blood sugar level from getting too high (hyperglycemia) or too low (hypoglycemia).

The cells in your body need sugar for energy. However, sugar cannot go into most of your cells directly. After you eat food and your blood sugar level rises, cells in your pancreas (known as beta cells) are signaled to release insulin into your bloodstream. Insulin then attaches to and signals cells to absorb sugar from the bloodstream. Insulin is often described as a “key,” which unlocks the cell to allow sugar to enter the cell and be used for energy.

People with type 1 diabetes cannot make insulin because the beta cells in their pancreas are damaged or destroyed. Therefore, these people will need insulin injections to allow their body to process glucose and avoid complications from hyperglycemia.

People with type 2 diabetes do not respond well or are resistant to insulin. They may need insulin shots to help them better process sugar and to prevent long-term complications from this disease. Persons with type 2 diabetes may first be treated with oral medications, along with diet and exercise. Since type 2 diabetes is a progressive condition, the longer someone has it, the more likely they will require insulin to maintain blood sugar levels.

Insulin can be given by a syringe, injection pen, or an insulin pump that delivers a continuous flow of insulin. The purpose of the Patient Guide to Insulin is to educate patients, parents, and caregivers about insulin treatment of diabetes.  

Diabetes causes injury to small blood vessels in the body.
When the blood vessels in the kidneys are injured, your kidneys cannot clean your blood properly. Your body will retain more water and salt than it should, which can result in weight gain and ankle swelling. You may have protein in your urine. Also, waste materials will build up in your blood.
Diabetes also may cause damage to nerves in your body. This can cause difficulty in emptying your bladder. The pressure resulting from your full bladder can back up and injure the kidneys. Also, if urine remains in your bladder for a long time, you can develop an infection from the rapid growth of bacteria in urine that has a high sugar level.
About 30 percent of patients with Type 1 (juvenile onset) diabetes and 10 to 40 percent of those with Type 2 (adult onset) diabetes eventually will suffer from kidney failure.
The earliest sign of diabetic kidney disease is an increased excretion of albumin in the urine. As your kidneys fail, your blood urea nitrogen (BUN) levels will rise as well as the level of creatinine in your blood which causes nausea, vomiting, a loss of appetite, weakness, increasing fatigue, itching, muscle cramps (especially in your legs) and anemia (a low blood count).

Diabetic retinopathy is caused by changes in the blood vessels of the retina, the thin, light-sensitive inner lining in the back of your eye. This damage, called retinopathy, occurs to small blood vessels in the retina, which are easily harmed by high levels of glucose in the blood. There are two stages of diabetic retinopathy—an initial stage, which is called nonproliferative retinopathy, and a more serious stage called proliferative retinopathy, in which there is a greater risk of hemorrhage into the vitreous or detachment of the retina leading to severe vision loss. Another condition, called diabetic macular edema, can occur with either stage.
In the early nonproliferative stage, high levels of blood glucose cause damage to the blood vessels in the retina. They actually can leak fluid, which can collect and cause the retina to swell. If fluid collects in the central part of the retina (macular edema), blurred vision may occur. Macular edema can be treated with laser surgery when central vision is threatened.
A more dangerous stage of eye disease from diabetes is proliferative retinopathy. During this stage, abnormal blood vessels grow over the surface of the retina. These fragile blood vessels may rupture and bleed into the vitreous humor, the clear gel that fills the center of the eye. With vitreous hemorrhage, the blood blocks the passage of light to the retina and loss of vision or even blindness may occur. A further problem can occur when these blood vessels cause scar tissue, which may pull on the retina and cause it to become detached from the back of the eye. About half of the people with proliferative retinopathy also have macular edema. Proliferative diabetic retinopathy can also be treated with laser surgery to preserve vision and reduce the risk of severe vision loss to less than 5%.  Additionally, vitreous hemorrhage that does not resolve, or scar tissue causing traction on the retina, can be removed by a surgical procedure called vitrectomy.
Elevated levels of blood glucose can damage the body in various ways, including harming the blood vessels in your eyes. Diabetes can affect the lining of the blood vessels in your eyes, causing them to thicken and develop leaks. Poor circulation in the retinal vessels can compound these problems by causing the production of fragile new vessels. To treat diabetic retinopathy, the doctor focuses the laser – a bright powerful beam of light – on the retina. The light scars the areas of the retina to stop the formation of new blood vessels and to shrink any new vessels that are present. The goal is not to make vision better, so most people with proliferative retinopathy can expect their vision to be about the same as before treatment. But their eyes are in much better health, because the laser treatment has halted the formation of new blood vessels.
 

Uncontrolled diabetes can lead to a number of short and long-term health complications, including hypoglycemia, heart disease, nerve damage and amputation, and vision problems. The majority of these diabetes-related conditions occur as a result of uncontrolled blood glucose levels, particularly elevated blood sugar over a prolonged period of time. It is common for most people with diabetes to begin to develop complications after having diabetes for a number of years.
With good diabetes control and living a healthy, active lifestyle, it is possible for people to go a number of decades complication free. The long-term measure of blood glucose is important for people with diabetes as the higher their HbA1c value, the greater the risk of developing serious diabetic complications.
By reducing HbA1c and keeping blood pressure and cholesterol levels well controlled, people with diabetes can reduce their risk of diabetic complications.

Possible complications include:
Cardiovascular disease: Diabetes dramatically increases the risk of various cardiovascular problems, including coronary artery disease with chest pain (angina), heart attack, stroke and narrowing of arteries (atherosclerosis). If you have diabetes, you are more likely to have heart disease or stroke.

Nerve damage (neuropathy):Excess sugar can injure the walls of the tiny blood vessels (capillaries) that nourish your nerves, especially in your legs. This can cause tingling, numbness, burning or pain that usually begins at the tips of the toes or fingers and gradually spreads upward. Left untreated, you could lose all sense of feeling in the affected limbs. Damage to the nerves related to digestion can cause problems with nausea, vomiting, diarrhea or constipation. For men, it may lead to erectile dysfunction.

Kidney damage (nephropathy): The kidneys contain millions of tiny blood vessel clusters (glomeruli) that filter waste from your blood. Diabetes can damage this delicate filtering system. Severe damage can lead to kidney failure or irreversible end-stage kidney disease, which may require dialysis or a kidney transplant.

Eye damage (retinopathy): Diabetes can damage the blood vessels of the retina (diabetic retinopathy), potentially leading to blindness. Diabetes also increases the risk of other serious vision conditions, such as cataracts and glaucoma.

Foot damage: Nerve damage in the feet or poor blood flow to the feet increases the risk of various foot complications. Left untreated, cuts and blisters can develop serious infections, which often heal poorly. These infections may ultimately require toe, foot or leg amputation.

Skin conditions:Diabetes may leave you more susceptible to skin problems, including bacterial and fungal infections.

Hearing impairment: Hearing problems are more common in people with diabetes.

Alzheimer's disease: Type 2 diabetes may increase the risk of Alzheimer's disease. The poorer your blood sugar control, the greater the risk appears to be. Although there are theories as to how these disorders might be connected, none has yet been proved.

Type 1 diabetes results from the destruction of insulin-producing cells in the islets of the pancreas. Islet cell transplantation involves extracting islet cells from the pancreas of a deceased donor and implanting them in the liver of someone with Type 1. This minor procedure is usually done twice for each transplant patient, and can be performed with minimal risk using a needle under local anaesthetic. Islet transplants have been shown to reduce the risk of severe hypos. Results from UK islet transplant patients showed that the frequency of hypos was reduced from 23 per person per year before transplantation to less than one hypo per person per year afterwards.

Islet transplants usually also lead to improved awareness of hypoglycaemia, less variability in blood glucose levels, improved average blood glucose, improved quality of life and reduced fear of hypos. Long-term results are good and are improving all the time. For example, the majority of transplant patients can now expect to have a functioning transplant after six years and some people have had more than 10 years of clinical benefit.

Post-transplantation diabetes mellitus (PTDM), also known as new-onset diabetes mellitus (NODM), occurs in 10–15% of renal transplant recipients and is associated with cardiovascular disease and reduced lifespan. In the majority of cases, PTDM is characterized by β-cell dysfunction, as well as reduced insulin sensitivity in liver, muscle and adipose tissue. Glucose-lowering therapy must be compatible with immunosuppressant agents, reduced glomerular filtration rate (GFR) and severe arteriosclerosis. Such therapy should not place the patient at risk by inducing hypoglycaemic episodes or exacerbating renal function owing to adverse gastrointestinal effects with hypovolaemia.

Symptoms of severe increased thirst, frequent urination, unexplained weight loss, increased hunger, tingling of your hands or feet indicates to run a test for diabetes.
To confirm the diagnosis of type 2 diabetes, your doctor will order a fasting plasma glucose test or casual plasma glucose. The fasting plasma glucose test (FPG) is the preferred method for diagnosing diabetes, because it is easy to do, convenient, and less expensive than other tests. Before taking the blood glucose test, you will not be allowed to eat anything for at least eight hours. During a blood glucose test, blood will be drawn and sent to a lab for analysis.
Normal fasting blood glucose -- or blood sugar -- is between 70 and 100 milligrams per deciliter or mg/dL for people who do not have diabetes. The standard diagnosis of diabetes is made when two separate blood tests show that your fasting blood glucose level is greater than or equal to 126 mg/dL.
The casual plasma glucose test is another method of diagnosing diabetes. During the test, blood sugar is tested without regard to the time since the person's last meal. You are not required to abstain from eating prior to the test.
A glucose level greater than 200 mg/dL may indicate diabetes, especially if the test is repeated at a later time and shows similar results.
The hemoglobin A1c test (also called the glycated hemoglobin test or HbA1c), is an important diabetes blood test used to determine how well your diabetes is being controlled. This diabetes test provides an average of your blood sugar control over a six- to 12-week period and is used in conjunction with home blood sugar monitoring to make adjustments in your diabetes medicines. The HbA1c level can also be used to diagnose diabetes if a value of equal to or greater than 6.5% is found.
Along with the hemoglobin A1c test, it's important for people with diabetes to have a dilated eye exam at least once a year as part of a complete eye exam. This important test can detect early signs of retinopathy, which may have no symptoms at first. A foot exam once or twice a year -- or at every doctor's visit -- is also imperative to detect decreased circulation and sores that may not be healing. Early detection of eye and foot problems in diabetes allows your doctor to prescribe proper treatment when it is most effective.

The main goal of diabetes management is, as far as possible, to restore carbohydrate metabolism to a normal state. To achieve this goal, individuals with an absolute deficiency of insulin require insulin replacement therapy, which is given through injections or an insulin pump. Insulin resistance, in contrast, can be corrected by dietary modifications and exercise. Other goals of diabetes management are to prevent or treat the many complications that can result from the disease itself and from its treatment.

Modification of adverse lifestyle factors is an important aspect of the management of all types of diabetes. In particular, appropriate management of cardiovascular risk factors such as smoking, physical inactivity and poor diet is important for the prevention of macrovascular disease. Microvascular complications may also be affected by adverse lifestyle factors, eg smoking. However, helping patients to modify certain behaviors should take account of other factors such as the patient’s willingness to change, their perception of their diabetes, and factors which may be indirectly related to their diabetes, such as depression and adverse effects on quality of life.

Drugs used in diabetes treat diabetes mellitus by lowering glucose levels in the blood. With the exceptions of Insulin, exenatide, liraglutide and pramlintide, all are administered orally and are thus also called oral hypoglycemic agents or oral antihyperglycemic agents. There are different classes of anti-diabetic drugs, and their selection depends on the nature of the diabetes, age and situation of the person, as well as other factors.
Diabetes mellitus type 1 is a disease caused by the lack of insulin. Insulin must be used in Type I, which must be injected.
Diabetes mellitus type 2 is a disease of insulin resistance by cells. Type 2 diabetes mellitus is the most common type of diabetes. Treatments include (1) agents that increase the amount of insulin secreted by the pancreas, (2) agents that increase the sensitivity of target organs to insulin, and (3) agents that decrease the rate at which glucose is absorbed from the gastrointestinal tract.
Several groups of drugs, mostly given by mouth, are effective in Type II, often in combination. The therapeutic combination in Type II may include insulin, not necessarily because oral agents have failed completely, but in search of a desired combination of effects. The great advantage of injected insulin in Type II is that a well-educated patient can adjust the dose, or even take additional doses, when blood glucose levels measured by the patient, usually with a simple meter, as needed by the measured amount of sugar in the blood.

Insulin sensitizers address the core problem in Type II diabetes—insulin resistance.

Thiazolidinediones (TZDs), also known as "glitazones," bind to PPARγ, a type of nuclear regulatory protein involved in transcription of genes regulating glucose and fat metabolism.
Secretagogues are drugs that increase insulin output from the pancreas. Meglitinides help the pancreas produce insulin and are often called "short-acting secretagogues".
Alpha-glucosidase inhibitors are "diabetes pills" but not technically hypoglycemic agents because they do not have a direct effect on insulin secretion or sensitivity. Dipeptidyl peptidase-4 (DPP-4) inhibitors increase blood concentration of the incretin GLP-1 by inhibiting its degradation by dipeptidyl peptidase-4. Glycosurics are SGLT-2 inhibitors block the re-uptake of glucose in the renal tubules, promoting loss of glucose in the urine.

The concept of 'new technologies' for type 1 diabetes and new discovery and advanced type 2 diabetes treatment has expanded in recent years at a rate that some might consider comparable to 'Moore’s Law', and the sheer number of new technologies entering into the type 1 diabetes marketplace is also growing at a remarkable rate. From the patient’s perspective, this is not only exciting but can lead to a sense of optimism. Technologies that today are growing commonplace (e.g. insulin pumps, rapid HbA1c monitoring, etc. come under new therapeutic mechanisms of diabetes. Indeed, it could be argued that the major advances in type 1 diabetes care made within the last quarter of a century have come from technology rather than biology. At the same time, not all new technologies succeed (e.g. the Glucowatch), regardless of their purported promise. Both type 1 diabetes patients and their healthcare providers will soon see a series of further advanced medical technologies used in hospital and new technologies and novel therapies in diabetes treatment whose basis is tied to the notion of improving the lives of those with the disease.
The aim of diabetes treatment is to keep, within reason, blood glucose levels as near to normal as possible. Training in self-management of diabetes forms an essential part of diabetes management. Treatment should be agreed on an individual basis and address medical, psychosocial and lifestyle issues.
A variety of different factors have a role to play in treating diabetes, but the importance of balanced, co-ordinated diabetes treatment for all diabetics cannot be underestimated.
Regular and successful treatment decreases the risk of each patient developing diabetes complications.

Three diabetes treatments with entirely new modes of action were approved: exenatide injection for people with type 2 diabetes, pramlintide injection as an add-on to insulin therapy for people with type 1 or type 2 diabetes and Sitagliptin also for people with type 2 diabetes. Some diabetes medications help the pancreas release more insulin (if you have type 2 diabetes), others help cells use insulin better, and others keep the liver from releasing too much glucose. The new treatments focus action on hormones called incretins.
Exenatide injection:

• is injected twice a day at mealtime
• is for those with type 2 diabetes who have been unable to control blood glucose with oral medicines
• improves blood glucose control by mimicking incretin hormones, stimulating insulin and slowing stomach-emptying
• leads to weight loss because patients will feel full faster and stop eating
• can cause nausea

Exenatide extended release  is  injected once per week is for those with type 2 diabetes who have been unable to control blood glucose with oral medicines  that helps to improves blood glucose control by mimicking incretin hormones, stimulating insulin and slowing stomach-emptying leads to weight loss because patients will feel full faster and stop eating which can cause nausea.

Pramlintide acetate is intended for those with type 1 or type 2 diabetes who use insulin

• is injected at mealtime
• is to never mix with insulin in one syringe; which creates the need for an additional injection for the patient
• used for better glucose control, reduction in blood glucose spikes, reduction in food intake, whichleads to weight loss
• can cause nausea or hypoglycemia (dangerously low blood glucose)

Sitagliptin Saxagliptin and linagliptin-All three of these pills

• are taken once a day
• are for type 2 diabetes
• do not promote weight gain
• are often used in combination with metformin
• have very little, if any, side effects
• Should be taken with caution for patients with renal disease (dose should be decreased)
• slows the breakdown of incretins, so insulin is released over a longer period of time