DIABETES MELLITUS

INTRODUCTION  

            Diabetes (diabetes mellitus) is classed as a metabolism disorder. Metabolism refers to the way our bodies use digested food for energy and growth. Most of what we eat is broken down into glucose. Glucose is a form of sugar in the blood - it is the principal source of fuel for our bodies. When our food is digested, the glucose makes its way into our bloodstream. Our cells use the glucose for energy and growth. However, glucose cannot enter our cells without insulin being present - insulin makes it possible for our cells to take in the glucose.

            Insulin is a hormone that is produced by the pancreas. After eating, the pancreas automatically releases an adequate quantity of insulin to move the glucose present in our blood into the cells, as soon as glucose enters the cells blood-glucose levels drop. A person with diabetes has a condition in which the quantity of glucose in the blood is too elevated (hyperglycemia). This is because the body either does not produce enough insulin, produces no insulin, or has cells that do not respond properly to the insulin the pancreas produces. This results in too much glucose building up in the blood. This excess blood glucose eventually passes out of the body in urine. So, even though the blood has plenty of glucose, the cells are not getting it for their essential energy and growth requirements.

            Diabetes comes from Greek, and it means a "siphon". Aretus the Cappadocian, a Greek physician during the second century A.D., named the condition diabainein. He described patients who were passing too much water (polyuria) - like a siphon. The word became "diabetes" from the English adoption of the Medieval Latin diabetes .In 1675, Thomas Willis added mellitus to the term, although it is commonly referred to simply as diabetes. Mel in Latin means "honey"; the urine and blood of people with diabetes has excess glucose, and glucose is sweet like honey. Diabetes mellitus could literally mean "siphoning off sweet water". In ancient China people observed that ants would be attracted to some people's urine, because it was sweet. The term "Sweet Urine Disease" was coined.

All types of diabetes are treatable.

            Diabetes type 1 lasts a lifetime, there is no known cure. Type 2 usually lasts a lifetime, however, some people have managed, through a lot of exercise, diet and excellent body weight control to get rid of their symptoms without medication. Patients with type 1 are treated with regular insulin injections, as well as a special diet and exercise.
            Patients with Type 2 diabetes are usually treated with tablets, exercise and a special diet, but sometimes insulin injections are also required.

DEFINITION

            Diabetes mellitus (DM) or simply diabetes, is a group of metabolic diseases in which a person has high blood sugar. This high blood sugar produces the symptoms of frequent urination, increased thirst, and increased hunger. Untreated, diabetes can cause many complications.      

 Types of Diabetes Mellitus:

            Diabetes is due to either the pancreas not produce enough insulin, or because cells of the body do not respond properly to the insulin that is produced. Diabetes mellitus refers to a group of diseases that affect how your body uses blood glucose, commonly called blood sugar. Glucose is vital to health because it's an important source of energy for the cells that make up muscles and tissues. It's also brain's main source of fuel. There are three main types of diabetes mellitus:

Ø  Type 1 DM

Ø  Type 2 DM 

Ø  Gestational diabetes  

Diabetes mellitus (or diabetes) is a chronic, lifelong condition that affects your body's ability to use the energy found in food.

            All types of diabetes mellitus have something in common. Normally, body breaks down the sugars and carbohydrates you eat into a special sugar called glucose. Glucose fuels the cells in body. But the cells need insulin, a hormone, in bloodstream in order to take in the glucose and use it for energy. With diabetes mellitus, either body doesn't make enough insulin, it can't use the insulin it does produce, or a combination of both.

Symptoms

Ø  Frequent urination

Ø  Increased thirst

Ø  Increased hunger.      

Complications                                                                                        

            Acute complications include diabetic ketoacidosis and nonketotic hyperosmolar coma. Serious long-term complications include heart disease, kidney failure, and damage to the eyes.

Prevention And Treatment

ü  Healthy diet

ü  Physical exercise

ü  Not using tobacco

ü  Normal body weight  

           Blood pressure control and proper foot care are also important in those with the disease. Type 1 diabetes must be managed with insulin injections. Type 2 diabetes may be treated with medications with or without insulin.

            Insulin and some oral medications can cause low blood sugar, which can be dangerous. Pancreas transplants have been tried in an effort to cure type 1 diabetes with limited success. Gastric bypass surgery has been successful in many with severe obesity and type 2 DM. Gestational diabetes usually resolves after delivery.   

SIGNS AND SYMPTOMS

Classic Symptoms

ü  Wight loss

ü  Polyuria (frequent urination)

ü  Polydipsia (increased thirst)

ü  Polyphagia(increased hunger)

Symptoms may develop rapidly (weeks or months) in type 1 diabetes, while they usually develop much more slowly and may be subtle or absent in type 2 diabetes.

            Prolonged high blood glucose can cause glucose absorption in the lens of the eye, which leads to changes in its shape, resulting in vision changes. Blurred vision is a common complaint leading to a diabetes diagnosis. A number of skin rashes that can occur in diabetes are collectively known as diabetic dermadromes.

Complications

v Damage to blood vessels

v Risk of cardiovascular disease

v Atherosclerosis

v Coronary artery disease

v Stroke

v Peripheral vascular disease

v Diabetic retinopathy

v Diabetic nephropathy

Complications linked to badly controlled diabetes:

Ø  Eye complications - glaucoma, cataracts, diabetic retinopathy, and some others.

Ø  Foot complications - neuropathy, ulcers, and sometimes gangrene which may require that the foot be amputated

Ø  Skin complications - people with diabetes are more susceptible to skin infections and skin disorders

Ø  Heart problems - such as ischemic heart disease, when the blood supply to the heart muscle is diminished

Ø  Hypertension - common in people with diabetes, which can raise the risk of kidney disease, eye problems, heart attack and stroke

Ø  Mental health - uncontrolled diabetes raises the risk of suffering from depression, anxiety and some other mental disorders

Ø  Hearing loss - diabetes patients have a higher risk of developing hearing problems

Ø  Gum disease - there is a much higher prevalence of gum disease among diabetes patients.

Ø  Ketoacidosis - a combination of ketosis and acidosis; accumulation of ketone bodies and acidity in the blood.

Ø  Neuropathy - diabetic neuropathy is a type of nerve damage which can lead to several different problems.

Ø  HHNS (Hyperosmolar Hyperglycemic Nonketotic Syndrome) - blood glucose levels shoot up too high, and there are no ketones present in the blood or urine. It is an emergency condition.

Ø  Nephropathy - uncontrolled blood pressure can lead to kidney disease

Ø  PAD (peripheral arterial disease) - symptoms may include pain in the leg, tingling and sometimes problems walking properly

Ø  Stroke - if blood pressure, cholesterol levels, and blood glucose levels are not controlled, the risk of stroke increases significantly

Ø  Erectile dysfunction - male impotence.

Ø  Infections - people with badly controlled diabetes are much more susceptible to infections

Ø  Healing of wounds - cuts and lesions take much longer to heal.

Prediabetes

            Prediabetes indicates a condition that occurs when a person's blood glucose levels are higher than normal but not high enough for a diagnosis of type 2 DM. Many people destined to develop type 2 DM spend many years in a state of prediabetes.

            The vast majority of patients with type 2 diabetes initially had prediabetes. Their blood glucose levels where higher than normal, but not high enough to merit a diabetes diagnosis. The cells in the body are becoming resistant to insulin. Studies have indicated that even at the prediabetes stage, some damage to the circulatory system and the heart may already have occurred.

The following is a comprehensive list of other causes of diabetes:

v Genetic defects of β-cell function

·        Maturity onset diabetes of the young

·        Mitochondrial DNA mutations

v Genetic defects in insulin processing or insulin action

·        Defects in proinsulin conversion

·        Insulin gene mutations

·        Insulin receptor mutations

v Exocrine pancreatic defects

·        Chronic pancreatitis

·        Pancreatectomy

·        Pancreatic neoplasia

·        Cystic fibrosis

·        Hemochromatosis

·        Fibrocalculous pancreatopathy

v Endocrinopathies

·        Growth hormone excess (acromegaly)

·        Cushing syndrome

·        Hyperthyroidism

·        Pheochromocytoma

·        Glucagonoma

v Infections

·        Cytomegalovirus infection

·        Coxsackievirus B

v Drugs

·        Glucocorticoids

·        Thyroid hormone

·        β-adrenergic agonists

·        Statins

DIABETES MELLITUS TYPE 1

            Diabetes mellitus type 1 (also known as type 1 diabetes, or T1DM; formerly insulin dependent diabetes or juvenile diabetes) is a form of diabetes mellitus that results from the autoimmune destruction of the insulin-producing beta cells in the pancreas. The subsequent lack of insulin leads to increased blood and urine glucose.

            The classical symptoms are polyuria(frequent urination), polydipsia (increased thirst), polyphagia (increased hunger), and weight loss.

            Untreated, type 1 diabetes is ultimately fatal; however, the disease can be controlled with supplemental insulin. Insulin is most commonly administered by injection at periodic intervals several times per day, though other options, such as insulin pumps, exist.

            Type 1 diabetes can be distinguished from type 2 by autoantibody testing - glutamic acid decarboxylase autoantibodies (GADA), islet cell autoantibodies (ICA), insulinoma-associated (IA-2) autoantibodies, and zinc transporter autoantibodies (ZnT8) are present in individuals with type 1 diabetes, but not type 2. The C-peptide assay, which measures endogenous insulin production, can also be used. Type 1 diabetes can lead to a number of complications, both in the short term and in the long term. Furthermore, complications may arise from both low blood sugar and high blood sugar, both due to the non-physiological manner in which insulin is replaced. Low blood sugar may lead to seizures or episodes of unconsciousness, and requires emergency treatment. In the short term, untreated type 1 diabetes can lead to diabetic ketoacidosis, and in the long term it can lead to eye damage, organ damage, etc.

            Type 1 diabetes is also called insulin-dependent diabetes. It used to be called juvenile-onset diabetes, because it often begins in childhood. Type 1 diabetes is an autoimmune condition. It's caused by the body attacking its own pancreas with antibodies. In people with type 1 diabetes, the damaged pancreas doesn't make insulin. This type of diabetes may be caused by a genetic predisposition. It could also be the result of faulty beta cells in the pancreas that normally produce insulin.

            A number of medical risks are associated with type 1 diabetes. Many of them stem from damage to the tiny blood vessels in your eyes (called diabetic retinopathy), nerves (diabetic neuropathy), and kidneys (diabetic nephropathy). Even more serious is the increased risk of heart disease and stroke.

            Treatment for type 1 diabetes involves taking insulin, which needs to be injected through the skin into the fatty tissue below. The methods of injecting insulin include:

•           Syringes

•           Insulin pens that use pre-filled cartridges and a fine needle

•           Jet injectors that use high pressure air to send a spray of insulin through the skin

•           Insulin pumps that dispense insulin through flexible tubing to a catheter under the skin of the abdomen

A periodic test called the A1C blood test estimates glucose levels in your blood over the previous three months. It's used to help identify overall glucose level control and the risk of complications from diabetes, including organ damage.

Having type 1 diabetes does require significant lifestyle changes that include:

•           Frequent testing of your blood sugar levels

•           Careful meal planning

•           Daily exercise

•           Taking insulin and other medications as needed

People with type 1 diabetes can lead long, active lives if they carefully monitor their glucose, make the needed lifestyle changes, and adhere to the treatment plan.

•           Type 1 DM results from the body's failure to produce insulin. This form was previously referred to as "insulin-dependent diabetes mellitus" (IDDM) or "juvenile diabetes".

Cause

 Environmental

            Environmental factors can influence expression of type 1. For identical twins, when one twin had type 1 diabetes, the other twin only had it 30%–50% of the time. Despite having exactly the same genome, one twin had the disease, whereas the other did not; this suggests environmental factors, in addition to genetic factors, can influence the disease's prevalence. Other indications of environmental influence include the presence of a 10-fold difference in occurrence among Caucasians living in different areas of Europe, and a tendency to acquire the incidence of the disease of the destination country for people who migrate.

Virus

            Type 1 diabetes is a virus-triggered autoimmune response in which the immune system attacks virus-infected cells along with the beta cells in the pancreas. The Coxsackie virus family or rubella is implicated, although the evidence is inconclusive. In type 1, pancreatic beta cells in the islets of Langerhans are destroyed, decreasing endogenous insulin production. This distinguishes type 1's origin from type 2. The type of diabetes a patient has is determined only by the cause—fundamentally by whether the patient is insulin resistant (type 2) or insulin deficient without insulin resistance (type 1).

            This vulnerability is not shared by everyone, for not everyone infected by the suspected virus develops type 1 diabetes. This has suggested presence of a genetic vulnerability and there is indeed an observed inherited tendency to develop type 1. It has been traced to particular HLA genotypes, though the connection between them and the triggering of an autoimmune reaction is still poorly understood.

Diet

            Some researchers believe the autoimmune response is influenced by antibodies against cow's milk proteins.

            Vitamin D in doses of 2000 IU per day given during the first year of a child's life has been connected in one study in northern Finland (where intrinsic production of Vitamin D is low due to low natural light levels) with an 80% reduction in the risk of getting type 1 diabetes later in life.

            Having a short breastfeeding period as well as short attendance at day care are associated with an elevated risk of type 1 diabetes in Czech children.

Chemicals and drugs

            Some chemicals and drugs preferentially destroy pancreatic cells. Pyrinuron (Vacor, N-3-pyridylmethyl-N'-p-nitrophenyl urea), a rodenticide introduced in the United States in 1976, selectively destroys pancreatic beta cells, resulting in type 1 diabetes after accidental or intentional ingestion. Vacor was withdrawn from the U.S. market in 1979, but is still used in some countries. Zanosar is the trade name for streptozotocin, an antibiotic and antineoplastic agent used in chemotherapy for pancreatic cancer; it also kills beta cells, resulting in loss of insulin production. Other pancreatic problems, including trauma, pancreatitis or tumors (either malignant or benign), can also lead to loss of insulin production.

Pathophysiology

            The pathophysiology in diabetes type 1 is a destruction of beta cells in the pancreas, regardless of which risk factors or causative entities have been present.

            Individual risk factors can have separate pathophysiological processes to, in turn, cause this beta cell destruction. Still, a process that appears to be common to most risk factors is an autoimmune response towards beta cells, involving an expansion of autoreactive CD4+ T helper cells and CD8+ T cells, autoantibody-producing B cells and activation of the innate immune system.

            Insulin is the principal hormone that regulates uptake of glucose from the blood into most cells (primarily muscle and fat cells, but not central nervous system cells). Therefore, deficiency of insulin or the insensitivity of its receptors plays a central role in all forms of diabetes mellitus.

            Humans are capable of digesting some carbohydrates, in particular those most common in food; starch, and some disaccharides such as sucrose, are converted within a few hours to simpler forms, most notably the monosaccharide glucose, the principal carbohydrate energy source used by the body. The rest are passed on for processing by gut flora largely in the colon. Insulin is released into the blood by beta cells (β-cells), found in the islets of Langerhans in the pancreas, in response to rising levels of blood glucose, typically after eating. Insulin is used by about two-thirds of the body's cells to absorb glucose from the blood for use as fuel, for conversion to other needed molecules, or for storage.

            Insulin is also the principal control signal for conversion of glucose to glycogen for internal storage in liver and muscle cells. Lowered glucose levels result both in the reduced release of insulin from the β-cells and in the reverse conversion of glycogen to glucose when glucose levels fall. This is mainly controlled by the hormone glucagon, which acts in the opposite manner to insulin. Glucose thus forcibly produced from internal liver cell stores (as glycogen) re-enters the bloodstream; muscle cells lack the necessary export mechanism. Normally, liver cells do this when the level of insulin is low (which normally correlates with low levels of blood glucose).

            Higher insulin levels increase some anabolic ("building up") processes, such as cell growth and duplication, protein synthesis, and fat storage. Insulin (or its lack) is the principal signal in converting many of the bidirectional processes of metabolism from a catabolic to an anabolic direction, and vice versa. In particular, a low insulin level is the trigger for entering or leaving ketosis (the fat-burning metabolic phase).

            If the amount of insulin available is insufficient, if cells respond poorly to the effects of insulin (insulin insensitivity or resistance), or if the insulin itself is defective, then glucose will not have its usual effect, so it will not be absorbed properly by those body cells that require it, nor will it be stored appropriately in the liver and muscles. The net effect is persistent high levels of blood glucose, poor protein synthesis, and other metabolic derangements, such as acidosis.

            When the glucose concentration in the blood is raised to about 9-10 mmol/L (except certain conditions, such as pregnancy), beyond its renal threshold (i.e. when glucose level surpasses the transport maximum of glucose reabsorption), reabsorption of glucose in the proximal renal tubuli is incomplete, and part of the glucose remains in the urine (glycosuria).   

            This increases the osmotic pressure of the urine and inhibits reabsorption of water by the kidney, resulting in increased urine production (polyuria) and increased fluid loss. Lost blood volume will be replaced osmotically from water held in body cells and other body compartments, causing dehydration and increased thirst.

   

DIABETES MELLITUS TYPE 2

            Diabetes mellitus type 2 (formerly noninsulin-dependent diabetes mellitus (NIDDM) or adult-onset diabetes) is a metabolic disorder that is characterized by hyperglycemia (high blood sugar) in the context of insulin resistance and relative lack of insulin. This is in contrast to diabetes mellitus type 1, in which there is an absolute lack of insulin due to breakdown of islet cells in the pancreas. The classic symptoms are excess thirst, frequent urination, and constant hunger. Type 2 diabetes makes up about 90% of cases of diabetes, with the other 10% due primarily to diabetes mellitus type 1 and gestational diabetes. Obesity is thought to be the primary cause of type 2 diabetes in people who are genetically predisposed to the disease.

            Type 2 diabetes is initially managed by increasing exercise and dietary changes. If blood sugar levels are not adequately lowered by these measures, medications such as metformin or insulin may be needed. In those on insulin, there is typically the requirement to routinely check blood sugar levels.

            Rates of type 2 diabetes have increased markedly since 1960 in parallel with obesity. As of 2010 there were approximately 285 million people diagnosed with the disease compared to around 30 million in 1985.Long-term complications from high blood sugar can include heart disease, strokes, diabetic retinopathy where eyesight is affected, kidney failure which may require dialysis, and poor blood flow in the limbs leading to amputations. The acute complication of ketoacidosis, a feature of type 1 diabetes, is uncommon, however hyperosmolar hyperglycemic state may occur.

Type 2 DM results from insulin resistance, a condition in which cells fail to use insulin properly, sometimes also with an absolute insulin deficiency. This form was previously referred to as non insulin-dependent diabetes mellitus (NIDDM) or "adult-onset diabetes".

Cause

            The development of type 2 diabetes is caused by a combination of lifestyle and genetic factors. While some of these factors are under personal control, such as diet and obesity, other factors are not, such as increasing age, female gender, and genetics. A lack of sleep has been linked to type 2 diabetes. This is believed to act through its effect on metabolism. The nutritional status of a mother during fetal development may also play a role, with one proposed mechanism being that of altered DNA methylation.

Lifestyle

            A number of lifestyle factors are known to be important to the development of type 2 diabetes, including obesity and overweight (defined by a body mass index of greater than 25), lack of physical activity, poor diet, stress, and urbanization. Excess body fat is associated with 30% of cases in those of Chinese and Japanese descent, 60-80% of cases in those of European and African descent, and 100% of cases in Pima Indians and Pacific Islanders. Those who are not obese often have a high waist–hip ratio.

            Dietary factors also influence the risk of developing type 2 diabetes. Consumption of sugar-sweetened drinks in excess is associated with an increased risk. The type of fats in the diet are also important, with saturated fats and trans fatty acids increasing the risk, and polyunsaturated and monounsaturated fat decreasing the risk. Eating lots of white rice appears to also play a role in increasing risk. A lack of exercise is believed to cause 7% of cases.

Genetics

            Most cases of diabetes involve many genes, with each being a small contributor to an increased probability of becoming a type 2 diabetic. If one identical twin has diabetes, the chance of the other developing diabetes within his lifetime is greater than 90%, while the rate for nonidentical siblings is 25–50%. As of 2011, more than 36 genes had been found that contribute to the risk of type 2 diabetes. All of these genes together still only account for 10% of the total heritable component of the disease. The TCF7L2 allele, for example, increases the risk of developing diabetes by 1.5 times and is the greatest risk of the common genetic variants. Most of the genes linked to diabetes are involved in beta cell functions.

            There are a number of rare cases of diabetes that arise due to an abnormality in a single gene (known as monogenic forms of diabetes or "other specific types of diabetes").

Medical Conditions

            There are a number of medications and other health problems that can predispose to diabetes. Some of the medications include: glucocorticoids, thiazides, beta blockers, atypical antipsychotics, and statins. Those who have previously had gestational diabetes are at a higher risk of developing type 2 diabetes. Other health problems that are associated include: acromegaly, Cushing's syndrome, hyperthyroidism, pheochromocytoma, and certain cancers such as glucagonomas. Testosterone deficiency is also associated with type 2 diabetes.

Pathophysiology

            Type 2 diabetes is due to insufficient insulin production from beta cells in the setting of insulin resistance. Insulin resistance, which is the inability of cells to respond adequately to normal levels of insulin, occurs primarily within the muscles, liver, and fat tissue. In the liver, insulin normally suppresses glucose release. However, in the setting of insulin resistance, the liver inappropriately releases glucose into the blood. The proportion of insulin resistance versus beta cell dysfunction differs among individuals, with some having primarily insulin resistance and only a minor defect in insulin secretion and others with slight insulin resistance and primarily a lack of insulin secretion.

            Other potentially important mechanisms associated with type 2 diabetes and insulin resistance include: increased breakdown of lipids within fat cells, resistance to and lack of incretin, high glucagon levels in the blood, increased retention of salt and water by the kidneys, and inappropriate regulation of metabolism by the central nervous system. However, not all people with insulin resistance develop diabetes, since an impairment of insulin secretion by pancreatic beta cells is also required.

GESTATIONAL DIABETES

            Gestational diabetes (or gestational diabetes mellitus, GDM) is a condition in which women without previously diagnosed diabetes exhibit high blood glucose levels during pregnancy (especially during their third trimester). There is some question whether the condition is natural during pregnancy. Gestational diabetes is caused when insulin receptors do not function properly. This is likely due to pregnancy-related factors such as the presence of human placental lactogen that interferes with susceptible insulin receptors. This in turn causes inappropriately elevated blood sugar levels.

            Gestational diabetes generally has few symptoms and it is most commonly diagnosed by screening during pregnancy. Diagnostic tests detect inappropriately high levels of glucose in blood samples. Gestational diabetes affects 3-10% of pregnancies, depending on the population studied, so may be a natural phenomenon. As with diabetes mellitus in pregnancy in general, babies born to mothers with untreated gestational diabetes are typically at increased risk of problems such as being large for gestational age (which may lead to delivery complications), low blood sugar, and jaundice. If untreated, it can also cause seizures or stillbirth. Gestational diabetes is a treatable condition and women who have adequate control of glucose levels can effectively decrease these risks. The food plan is often the first recommended target for strategic management of GDM.

            Women with unmanaged gestational diabetes are at increased risk of developing type 2 diabetes mellitus (or, very rarely, latent autoimmune diabetes or Type 1) after pregnancy, as well as having a higher incidence of pre-eclampsia and Caesarean section; their offspring are prone to developing childhood obesity, with type 2 diabetes later in life. Most women are able to manage their blood glucose levels with a modified diet and the introduction of moderate exercise, but some require antidiabetic drugs, including insulin.

            Gestational diabetes is formally defined as "any degree of glucose intolerance with onset or first recognition during pregnancy". This definition acknowledges the possibility that a woman may have previously undiagnosed diabetes mellitus, or may have developed diabetes coincidentally with pregnancy. Whether symptoms subside after pregnancy is also irrelevant to the diagnosis. A woman is diagnosed of having gestational diabetes when the glucose intolerance continues beyond 24-28 weeks of gestation.

Risk factors

Classical risk factors for developing gestational diabetes are:

Polycystic Ovary Syndrome.

A previous diagnosis of gestational diabetes or prediabetes, impaired glucose tolerance, or impaired fasting glycaemia.

Maternal age – a woman’s risk factor increases as she gets older {especially for women over 35 years of age}.

Previous poor obstetric history.

A previous pregnancy which resulted in a child with a macrosomia {high birth weight:>90^th centile or >4000 g{8 lbs 12.8 oz }

 Other genetic risk factors: There are at least 10 genes where certain polymorphism are associated with an increased risk of gestational diabetes.

            In addition to this, statistics show a double risk of GDM in smokers. About 40-60% of women with GDM have no demonstrable risk factor; for this reason many advocate to screen all women. But some women may demonstrate increased thirst, increased urination, fatigue, nausea and vomiting, bladder infection, yeast infections and blurred vision.

Prevention

            Theoretically, smoking cessation may decrease the risk of gestational diabetes among smokers. Physical exercise has not been found to have a significant effect of primary prevention of gestational diabetes in randomized controlled trials. It may be effective as tertiary prevention for women who have already developed the condition.

Pathophysiology

            Effect of insulin on glucose uptake and metabolism. Insulin binds to its receptor (1) On the cell membrane which in turn starts many protein activation cascades

(2) These include: translocation of Glut-4 transporter to the plasma membrane and influx    of glucose

(3) Glycogen synthesis

 (4) Glycolysis

 (5) and fatty acid synthesis

            Regular blood samples can be used to determine HbA1c levels, which give an idea of glucose control over a longer time period.          

Diagnosis

·         Fasting plasma glucose level ≥ 7.0 mmol/l (126 mg/dl)

·         Plasma glucose ≥ 11.1 mmol/l (200 mg/dL) two hours after a 75 g oral glucose load as in a glucose tolerance test

·         Symptoms of hyperglycemia and casual plasma glucose ≥ 11.1 mmol/l (200 mg/dl)

·         Glycated hemoglobin (Hb A1C) ≥ 6.5%.

            The rare disease diabetes insipidus has similar symptoms to diabetes mellitus, but without disturbances in the sugar metabolism (insipidus means "without taste" in Latin) and does not involve the same disease mechanisms.

Diabetes Mellitus Treatment & Management

            Diabetes mellitus is a chronic disease, for which there is no known cure except in very specific situations. Management concentrates on keeping blood sugar levels as close to normal ("euglycemia") as possible, without causing hypoglycemia. This can usually be accomplished with diet, exercise, and use of appropriate medications (insulin in the case of type 1 diabetes; oral medications, as well as possibly insulin, in type 2 diabetes).

            Patient education, understanding, and participation is vital, since the complications of diabetes are far less common and less severe in people who have well-managed blood sugar levels. The goal of treatment is an HbA1C level of 6.5%, but should not be lower than that, and may be set higher. Attention is also paid to other health problems that may accelerate the deleterious effects of diabetes. These include smoking, elevated cholesterol levels, obesity, high blood pressure, and lack of regular exercise. Specialised footwear is widely used to reduce the risk of ulceration, or re-ulceration, in at-risk diabetic feet. Evidence for the efficacy of this remains equivocal, however.     

            The goals in caring for patients with diabetes mellitus are to eliminate symptoms and to prevent, or at least slow, the development of complications. Microvascular (ie, eye and kidney disease) risk reduction is accomplished through control of glycemia and blood pressure; macrovascular (ie, coronary, cerebrovascular, peripheral vascular) risk reduction, through control of lipids and hypertension, smoking cessation, and aspirin therapy; and metabolic and neurologic risk reduction, through control of glycemia.

            Diabetes care is best provided by a multidisciplinary team of health professionals with expertise in diabetes, working in collaboration with the patient and family. Management includes the following:

•           Appropriate goal setting

•           Dietary and exercise modifications

•           Medications

•           Appropriate self-monitoring of blood glucose (SMBG)

•           Regular monitoring for complications

•           Laboratory assessment

Ideally, blood glucose should be maintained at near-normal levels (preprandial levels of 90-130 mg/dL and hemoglobin A1C [HbA1c] levels < 7%). However, focus on glucose alone does not provide adequate treatment for patients with diabetes mellitus. Treatment involves multiple goals (ie, glycemia, lipids, blood pressure).

            Aggressive glucose lowering may not be the best strategy in all patients. Individual risk stratification is highly recommended. In patients with advanced type 2 diabetes who are at high risk for cardiovascular disease, lowering HbA1c to 6% or lower may increase the risk of cardiovascular events.

            A study from the ACCORD Study Group found that setting the treatment target for HbA1c below 6% in high-risk patients resulted in reduced 5-year nonfatal myocardial infarctions. However, patients who did not achieve the treatment target experienced increased 5-year mortality.

            Review of blood glucose logs must be part of any diabetes management plan. Both iron and erythropoietin treatments commonly prescribed in patients with chronic kidney disease cause a significant increase in HbA1c without affecting blood glucose levels.

            With each health-care system encounter, patients with diabetes should be educated about and encouraged to follow an appropriate treatment plan. Adherence to diet and exercise should continue to be stressed throughout treatment, because these lifestyle measures can have a large effect on the degree of diabetic control that patients can achieve.

            A study by Morrison et al found that more frequent visits with a primary care provider (every 2 wk) led to markedly rapid reductions in serum glucose, HbA1c, and low-density lipoprotein (LDL) cholesterol levels. However, how such a strategy can work globally remains a challenge due to available resources and economic restrictions.

The United Kingdom Prospective Diabetes Study

            The care of patients with type 2 diabetes mellitus has been profoundly shaped by the results of the United Kingdom Prospective Diabetes Study (UKPDS). This landmark study confirmed the importance of glycemic control in reducing the risk for microvascular complications and refuted previous data suggesting that treatment with sulfonylureas or insulin increased the risk of macrovascular disease. Major findings of the UKPDS are displayed in the images below.

Significant implications of the UKPDS findings include the following:

•           Microvascular complications (predominantly indicated by the need for laser photocoagulation of retinal lesions) are reduced by 25% when mean HbA1c is 7%, compared with 7.9%

•           A continuous relationship exists between glycemia and microvascular complications, with a 35% reduction in risk for each 1% decrement in HbA1c; a glycemic threshold (above the upper limit of normal for HbA1c) below which risk for microvascular disease is eliminated does not appear to exist

•           Glycemic control has minimal effect on macrovascular disease risk; excess macrovascular risk appears to be related to conventional risk factors such as dyslipidemia and hypertension

Sulfonylureas and insulin therapy do not increase macrovascular disease

•           Risk

•           Metformin reduces macrovascular risk in patients who are obese.

       Tests for Glucose (Sugar) and HbA1c

                If your blood glucose (sugar) level remains high then you have diabetes. If the level goes too low then you have hypoglycaemia.

     Urine test for glucose

              Urine (produced by the kidneys) does not normally contain glucose. The kidneys filter our blood, keeping substances the body needs while getting rid of waste products. Your kidneys constantly reabsorb glucose so that it doesn't enter your urine. However, if the blood glucose level goes above a certain level, the kidneys can't reabsorb all of the glucose. This means that some glucose will 'spill' through the kidneys into the urine.

            A simple dipstick test can detect glucose in a sample of urine. In a dipstick test a doctor or nurse uses a special chemical strip which he/she dips into a sample of your urine. Colour changes on the strip show whether there is glucose in the urine sample. If you have glucose in your urine, you are likely to have diabetes.

           However, some people have kidneys that are more 'leaky', and glucose may leak into urine with a normal blood level. Therefore, if your urine contains any glucose, you should have a blood test to measure the blood level of glucose to confirm, or rule out, diabetes.

Blood tests for glucose

Random blood glucose level

            A sample of blood taken at any time can be a useful test if diabetes is suspected. A level of 11.1 mmol/L or more in the blood sample indicates that you have diabetes. A fasting blood glucose test may be done to confirm the diagnosis.

Fasting blood glucose level

            A glucose level below 11.1 mmol/L on a random blood sample does not rule out diabetes. A blood test taken in the morning before you eat anything is a more accurate test. Do not eat or drink anything except water for 8-10 hours before a fasting blood glucose test. A level of 7.0 mmol/L or more indicates that you have diabetes.

            If you have no symptoms of diabetes (see the separate leaflet called Type 2 Diabetes) but the blood test shows a glucose level of 7.0 mmol/L or more then the blood test must be repeated to confirm you have diabetes. If you do have symptoms and the blood test shows a glucose level of 7.0 mmol/L or more then the test does not need to be repeated.

Oral glucose tolerance test

            This test may be done if the diagnosis of diabetes is in doubt. For this test, you fast overnight. In the morning you are given a drink which contains 75 g of glucose. A blood sample is taken two hours later. Normally, your body should be able to deal with the glucose and your blood level should not go too high. A glucose level of 11.1 mmol/L or more in the blood sample taken after two hours indicates that you have diabetes.

Home monitoring

            A drop of blood from a finger prick is placed on a test strip which has a chemical impregnated which reacts with glucose. By using a colour chart or a small glucose meter machine, the blood level of glucose can be measured quickly.

The HbA1c blood test

            If you have diabetes, your HbA1c level may be done every 2-6 months by your doctor or nurse. This test measures your recent average blood glucose level. The test measures a part of the red blood cells. Glucose in the blood attaches to part of the red blood cells. This part can be measured and gives a good indication of your average blood glucose over the previous 2-3 months.

            For people with diabetes, treatment aims to lower the HbA1c level to below a target level which is usually agreed between you and your doctor. Ideally, the aim is to maintain your HbA1c to less than 48 mmol/mol (6.5%) but this may not always be possible to achieve and the target level of HbA1c should be agreed on an individual basis between you and your doctor. (For example, by increasing the dose of medication, improving your diet, etc.)

            It is now recommended that HbA1c can also be used as a test to diagnose diabetes. An HbA1c value of 48 mmol/mol (6.5%) or above is recommended as the blood level for diagnosing diabetes.

The A1C test
            - at least 6.5% means diabetes
            - between 5.7% and 5.99% means prediabetes
            - less than 5.7% means normal

The FPG (fasting plasma glucose) test
            - at least 126 mg/dl means diabetes
            - between 100 mg/dl and 125.99 mg/dl means prediabetes
            - less than 100 mg/dl means normal

An abnormal reading following the FPG means the patient has impaired fasting glucose (IFG)

The OGTT (oral glucose tolerance test)
            - at least 200 mg/dl means diabetes
            - between 140 and 199.9 mg/dl means prediabetes
            - less than 140 mg/dl means normal.

Prevention

            There is no known preventive measure for type 1 diabetes. Type 2 diabetes can often be prevented by a person being a normal body weight and physical exercise.

New Developments in the Treatment of Type 2 Diabetes Mellitus

            Diabetes, a progressive disease of the endocrine system with a significant economic burden, is estimated to affect more than 371 million people worldwide   and over 24 million Americans in 2012. In 2011, 4.6 million deaths could be attributed to diabetes, and diabetes healthcare expenditures, including costs to the healthcare system and the patient, were at least 465 billion US dollars, of which 11% of total healthcare expenditures were from adults aged 20 to 79 years, and 75% of that cost was spent on those aged 50 to 79 years.

            Current American Diabetes Association (ADA) Standards of Care recommend metformin for pharmacologic management of type 2 diabetes mellitus (T2DM),  if no contraindications are present, at the time of diagnosis. If therapeutic goals are not met with monotherapy at maximal doses, a second oral agent, such  as a glucagon-like peptide-1 (GLP-1) agonist or insulin, are recommended for addition. For patients who are newly diagnosed, markedly symptomatic upon diagnosis, and/or have markedly elevated blood glucose or glycated hemoglobin (A1C) levels, initial pharmacologic therapy with insulin should be considered, with or without the addition of other agents.

            The current classes of medications that are available to treat T2DM include biguanides, sulfonylureas, meglitinides, thiazolidinediones (TZDs), alpha glucosidase inhibitors, dipeptidyl peptidase-IV (DPP-4) inhibitors, GLP-1 agonists, bile acid sequestrants, dopamine-2 agonists, and insulin. Although these agents are effective initially, glucose-lowering effects are not typically sustained long term as beta cell dysfunction progresses. Therefore, newer agents that are able to lower glucose long term without causing hypoglycemia, delay decline in beta cell dysfunction, assist with weight loss, and have beneficial effects on  cardiovascular disease need to be developed. It is important to acknowledge that, in addition to the aforementioned therapeutic effects, adverse effects must be  minimized.

            Several new classes of medications are currently in development, as well as a new long-acting insulin.

      Sodium-Glucose Cotransporter-2 Inhibitors (SGLT-2)

            SGLT-2, a low-affinity but high-capacity transporter found in the brush border of the proximal tubule, is a mediator of glucose reabsorption in the kidneys.  The kidneys contribute to glucose homeostasis via renal gluconeogenesis, glucose utilization, and reabsorption from glomerular filtration.3,4 Data suggest  that renal gluconeogenesis, renal glucose uptake, and renal glucose reabsorption are all increased in patients with T2DM due to the upregulation of  SGLT-2.5 In essence, SGLT-2 inhibitors exert their effects by causing the kidneys to excrete glucose into the urine. The effects are also independent of  insulin secretion.

            These proposed mechanisms make SGLT-2 a viable target to help combat hyperglycemia in patients with T2DM. A review of the literature,  conducted through a PubMed search of SGLT-2 inhibitors through April 2012, found that these agents decreased A1C anywhere from 0.5 to 1.5%, promoted  weight loss, and demonstrated low incidences of hypoglycemia. Incidence of adverse effects with these agents has been low with no severe episodes of hypoglycemia documented. The most common adverse effects reported with these agents were urinary tract infections (UTIs) and/or genital tract infections.

DIABETIC DIET

            If you have diabetes, your body cannot make or properly use insulin. This leads to high blood glucose, or blood sugar, levels. Healthy eating helps keep your blood sugar in your target range. It is a critical part of managing your diabetes, because controlling your blood sugar can prevent the complications of diabetes.  A registered dietitian can help make an eating plan just for you. It should take into account your weight, medicines, lifestyle, and other health problems you have.

Healthy diabetic eating include:

v Limiting foods that are high in sugar

v Eating smaller portions, spread out over the day

v Being careful about when and how many carbohydrates you eat

v Eating a variety of whole-grain foods, fruits and vegetables every day

v Eating less fat  

v Limiting your use of alcohol

v Using less salt

YOGA & DIABETES

            Diabetes Mellitus is a disease related to the impaired glucose tolerance of the body, insulin functioning is affected. Symptoms of diabetes can be excessive thirst, excessive hunger or excessive / frequent urination.

Type 1 diabetes is caused by No production of insulin and this is very difficult to treat with Yoga.

Type 2 diabetes which is caused by life style, stress related diseases can be effectively treated with Yoga.

Sun Salutation

            Sun Salutation is very good exercise for people suffering from diabetes, it increases the blood supply to various parts of body, improving insulin administration in the body, it gives all the benefits of exercise if practiced at 4 rounds per minute. If practiced at slow speed, it offers the benefits of asanas.

Asanas

            Asanas are beneficial in treatment of diabetes. Important aspect of Asanas is stability and comfort experienced in the position. After attaining the position, one needs to relax all the muscles and try to maintain the positions for long. Due to various twists, stretches and strains in the body, the internal organs are stretched and subjected to strain. This increases the blood supply, oxygen supply to the organs increasing the efficiency and functioning of the organ. Stretching various glands result in increased efficiency of the endocrine system. Asanas like Dhanurasana (Bow pose in prone position), Ardhamatsyendrasana (Half spinal twist), Vajrasana Yoga Mudra, Pavan Muktasana, Sarvangasana, Halasana, Matsyasana have been found useful in diabetes. These asanas have positive effect on pancreas and also insulin functioning. But to get this result, one needs to maintain the asana for longer duration while relaxing the muscles.

Pranayama

            There are 8 types of Pranayama mentioned in Hatha Yoga. One of the basic preparations for Pranayama is Nadi Shodhan Pranayama or alternate nostril breathing, this type is found useful in diabetes as Alternate nostril breathing has calming effect on nervous system, which reduces stress levels, helping in diabetes treatment. Also research has shown that Bhramari and Bhasrika Pranayama help in diabetes. Bharamari has calming effect on mind, brain and nervous system. Bhasrika Pranayama is revitalizing Pranayama, which increases oxygen levels and reduces carbon dioxide levels in the blood. In bhasrika Pranayama, the abdominal muscles and diaphragm are used which puts pressure on the internal organs. But before practicing these Pranayama, one must learn and practice deep breathing, fast breathing, alternate nostril breathing, Bandhas (Jalandhar bandha or chin lock, moola bandha and Uddiyan bandha or abdominal lock) from expert Guru.

                                 
Meditation

            Practice of meditation is especially useful in management of stress. Relaxed and Concentrated state of mind is the aim of any form of meditation which creates calming effect on nervous system, brings balance between Sympathetic and Parasympathetic nervous systems. Initially meditation may be difficult, and one can practice Omkar Chanting, concentration on breathing. Especially for diabetes, concentration on pancreas during the meditation practice has shown positive effects on sugar levels. One can even visualize the proper functioning of pancreas, proper insulin administration in the body can help in treatment of diabetes.

Yoga Nidra

            Yoga Nidra is very important process of deep relaxation, it helps alleviate the stress and has very good positive effects on the entire body - mind complex.

Cleansing Processes

            Master cleansing or Shankha Prakshalana is recommended for diabetes, complete Shankha Prakshalana takes 1 day and is recommended once in 6 months, but smaller version of it can be done 3 times a week. This process cleanses the Gastro Intestinal tract completely. This process is done by drinking 2 glasses of warm, salty water and lemon juice is added to it. Then performing 6 different exercises, this exercises speed up the peristaltic movements and one needs to evacuate bowels. In 2 hours about 7 to 8 bowels are completed till the clear water is evacuated.

Hydrotherapy

            Hydrotherapy plays a vital role in improving the metabolic rate and controlling the blood sugar level. A warm water enema cleanses the accumulated toxins from the colon, thereby detoxifies the system. Other treatments include Hip bath, immersion bath, Foot and Arm bath, steam bath, Gastro hepatic pack, hot and cold compress over abdomen, abdomen pack etc. These treatments enhance the capability of the muscles to utilize the blood sugar and increase blood flow to the muscles and provide better sleep.

Mud Therapy

            Mud therapy helps to correct the imbalance of the digestive and endocrinal organs, which remain under -active in diabetic patients resulting in accumulation of toxins. Full Mud bath is the best way to eliminating the toxins. Direct mud or mud pack on the abdomen are also found beneficial in this treatment. It increases the circulation, relieves inner congestion and elimination of morbid matter.

Massage Therapy

            Massage otherwise called a passive exercise is highly beneficial for improving the activities of circulatory, musculature, lymphatic & nervous system. It reduce the muscle tension and reduces the stress. Pancreatic massage proves to be beneficial in this condition.

Yoga Therapy

            Along with well balanced diet and nature cure treatment, Yoga should be done for good control of blood sugar level. Asanas, specifically useful to improve functions of the liver, digestive system and pancreas are beneficial in treating diabetes. Merudantasna (utthitapadasana), Vipareeta karani Mudra, Halasana, Vakrasana, Surya Namaskar, Kati Chakrasana, Udhva Hstottansana, Pada hastasana, Trikonasana, Pavanamuktasana, Chakrasana, Sarvangasna, Bhujangasana, Dhanurasana, Vajrasana, Ardha Matsyndrasana, Ushtrasana, Paschimottanasana, Mandukasna, Mayurasana, Matsyasana, Shavasana & sukhshma Vyayamas in case of obesity patients are beneficial.

Kriyas

            Neti, Vaman or Vastra dhauti, Kapalbhanti, Nauli and Agnisara are also highly beneficial.

Pranayama

            Anulom-Vilom, Ujjayi, Bharamari (minimum 10 rounds of each), Bhastrika and Suryabhedana Pranayama give much benefit. As tension is always associated with these patients, practice of relaxation techniques and Meditation (10 to 20 minutes) will be of great use.

Walking & Exercise

            A study done by New Castle University has shown that a 45 minutes daily walk can help to control sugar and helps your cells accept insulin more efficiently.

Regular exercise is important as part of a healthy life style. It greatly increases the expenditure of blood glucose as it is used while activity.

Sun Bath

            For better metabolic activity, sun bath for 20-40 minutes in the morning daily. Similarly, it should be done to the abdomen just below the left rib cage, the North Pole in the front and the South Pole opposite at the back for 15 minutes in the evening. In addition to that magnetized water should be taken four times daily.

Chromo Therapy

            Diabetes is treated by using yellow and green colours. Yellow colour stimulates the pancreas and green colour stimulates the thyroid gland which helps in elimination of toxins. Stress increases the body's production of adrenalin, which raises the blood sugar level. Reducing stress through Naturopathic treatments and Yoga will help to restore regular, healthy sleeping pattern which will help to keep the blood sugar level in control.