ISSN: 2455-281X

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ASIO Journal of Pharmaceutical & Herbal Medicines Research (ASIO-JPHMR)

Volume 3, Issue 1, 2017, 07-19

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PATHOPHYSIOLOGY OF DIABETES: A REVIEW

Sakshi Minocha1†, Saptarshi Das2

1 Department of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, Jayoti Vidyapeeth Women’s University,

Jaipur, Rajasthan, India.

2 Department of Pharmaceutical Sciences, Bengal College of Pharmaceutical Sciences and Research, Durgapur, West

Bengal, India.

ARTICLE INFO ABSTRACT

Review Article History Received: 17th June, 2017 Accepted: 05th August, 2017

Corresponding Author: † Sakshi Minocha

Department of Pharmaceutical

Sciences, Faculty of

Pharmaceutical Sciences, Jayoti

Vidyapeeth Women’s University,

Jaipur, Rajasthan, India

The ubiquity of diabetes is rapidly rising all over the globe at an alarming rate. Over the last three decades, the status of diabetes has been changed, earlier it was considered as a mild disorder of the elderly people. Now it becomes a major cause affecting the youth and middle aged people. Diabetes insipidus (DI) is a complex disease. It is inability of the body to conserve water. Polydipsia and polyuria are the major manifestations of DI. The proper management of DI is the replenishment of water loss. The best management for primary polydipsia is fluid restriction while fluid intake is used for adipsic diabetes insipidus. Diabetes mellitus is an endocrinological or metabolic disorder with an increasing global prevalence and incidence. High blood glucose levels are symptom of diabetes mellitus. It is associated with metabolic complications that can subsequently lead to premature death. The most disturbing trend is the shift in age of onset of diabetes to a younger age in the recent years. It is necessary to identify the diabetic patients at the earliest and provide appropriate lifestyle changes in preventing the onset of diabetes.

Keywords: polydipsia, insulin, glucose, Diabetes insipidus, polyuria.

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E-mail: saksmin7@gmail.com

INTRODUCTION Diabetes is the name given to a group with different conditions in which there is too much glucose in the blood. The pancreas either cannot make insulin or the insulin

produce is not enough and cannot work properly. Without insulin glucose binds in the blood leading to high blood glucose levels which can lead to complications.

Figure 1: Comparision of Diabetes insipidus and mellitus

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DIABETES INSIPIDUS The word “Diabetes Insipidus” is a combination of two words “Diabetes” and “Insipidus”. Diabetes is a word of Greek origin which means “siphon” and Insipidus of Latin

origin which means “without taste”. It is inappropriate secretion of anti-diuretic hormone (ADH) and characterized by polyuria and polydipsia.

Figure 2: Diabetes insipidus

CAUSES Kidneys filter all blood many times. Most of the water is reabsorbed, and only a small amount of concentrated urine is excreted. Diabetes insipidus (DI) occurs when the kidneys cannot concentrate the urine normally, and a large amount of dilute urine is excreted. The amount of water excreted in the urine is controlled by antidiuretic hormone (ADH). DI caused by a lack of ADH is called central diabetes insipidus. When DI is caused by a failure of the kidneys to respond to ADH, the condition is called nephrogenic diabetes insipidus. Nephrogenic means related to the kidney. Central DI can be caused by damage to the hypothalamus or pituitary gland as a result of: Genetic problems Head injury Infection Loss of blood supply to the pituitary gland Surgery Tumors in or near the pituitary TYPES OF DIABETES INSIPIDUS (DI): The Diabetes insipidus include following types: 1. Neurogenic diabetes insipidus 2. Nephrogenic diabetes insipidus 3. Gestational diabetes insipidus 4. Adipsic diabetes insipidus 5. Primary polydipsia 6. Dipsogenic diabetes insipidus 7. Psychogenic diabetes insipidus Neurogenic diabetes insipidus: It is most commonly

known as Central Diabetes Insipidus (CDI). It is characterized by insensitivity of the kidneys to ADH. In CDI person is unable to conserve water due to decreased synthesis of anti-diuretic hormone (ADH).

Etiology: The major cause of CDI is traumatic brain injury which leads to the damage of hypothalamo-neurohypophyseal region. It can also be due to Surgery and tumors of supraoptic and paraventricular nuclear region. The other causes are autoimmunity, histocytosis, granulomatosis, sarcodosis and alcohol. Clinical presentations: Polyuria and polydipsia are the main clinical manifestations. High production of urine leads to high plasma osmolality, hypernatremia and severe dehydration. Osteopenia also occurs due to diminished effect of prostaglandins and osteoblasts.

Nephrogenic diabetes insipidus: Nephrogenic diabetes Insipidus (NDI) is due to the insensitivity of kidneys in response to ADH, sensitivity to ADH decreases, polyuria increases. Etiology: mutations of V2 receptor gene (X-linked), aquaporin-2 (AQP2) gene and urea transporter-B gene are the causes of NDI. Drugs characterized as the causing agents of NDI are- Lithium, Amphotericin B, Colchicines, Gentamicin, Methoxyflurane and Demaclocycline. Its causes include - chronic renal failure, pyelonephritis, polycystic kidney disease, renal transplantation, chronic hypokalemia and chronic hypercalcemia. Clinical Presentation: Due to the ADH insensitivity polyuria increases. It also includes nocturia. Osmotic diuresis, leads to hyperchloremia, constipation and can cause mental retardation, seizures and death.

Gestational diabetes insipidus: Gestational diabetes insipidus (GDI) is less frequent and occurs only in pregnant women. Etiology: Placenta produces a Vasopressinase. It degrades the ADH and oxytocin. It catabolizes almost 99% quantity of produced oxytocin and ADH leading to GDI.

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Clinical Presentation: The most common are Polydipsia, polyuria and severe thirst. The association of GDI with preeclampsia and HELLP syndrome (hemolysis, elevated liver enzymes, low platelet count) is most commonly observed.

Adipsic diabetes insipidus: Adipsia is a disease in which there is an absence of thirst, dehydration and high plasma osmolality. It is also associated with CDI because it affects the supraoptic and pavaventricular region. Etiology: The main cause of ADI is the lesion of thirst center located in hypothalamus. Craniopharyngiomas affecting both thirst center and supraoptic and paraventricular region are important in causing the ADI. Clinical Presentation: Lack of thirst sensation with high plasma osmolality. High sodium level also causes lethargy, mental disturbances, and even death.

Primary polydipsia: Primary polydipsia (PP) is characterized by large amount of fluid intake. It leads to the low plasma osmolality and the production of ADH stops. It is divided into 2 sub-variants:

Dipsogenic diabetes insipidus: Dipsogenic diabetes Insipidus (DDI) is caused by the defect in person’s thirst center located in the hypothalamus.

Psychogenic diabetes insipidus: It is mainly caused

by psychiatric disorders like schizophrenia. It leads increase in fluid intake and excretion of highly dilute urine. Clinical Presentation: Hypotonic polyuria is common cause of PP. It also includes polydipsia, intermittent hyponatremia and psychosis; Hyponatremia can be fatal and cause death. DIFFERENTIAL DIAGNOSIS For the confirmation of polyuria, the urine output should be greater than 40ml/kg/24hrs.For the confirmation of DI urine osmolality should be <300 mOsm/kg. For the confirmation Water Deprivation Test is performed. For this test person should be dehydrated to stimulate ADH production and measure the volume and osmolality with each discharge until the weight decreases by 3% or plasma sodium level reaches 145mmol/L.Then treat with desmopressin.

If the concentration of urine rises by 50% then person is suffering from CDI

If it increases by <10% then the diagnosis is NDI. If the osmolality increases more than 750 mOsm then

the patient is suffering from either CDI or PP. COMPLICATIONS OF DIABETES INSIPIDUS

1. Dehydration: In diabetes insipidus, body will find it difficult to retain enough water, even after drinking fluid constantly. This can lead to dehydration .It include:

dizziness or light-headedness headache dry mouth and lips

sunken features (particularly the eyes) confusion and irritability

Dehydration can be treated by rebalancing the level of water in your body.

2. Electrolyte imbalance: Diabetes insipidus also cause an electrolyte imbalance. Body loses too much water; the concentration of these electrolytes rises. This dehydration disrupts other functions of the body, such as the way muscles work. It can also lead to:

headache fatigue irritability muscle pain

SYMPTOMS:

Pass pale, watery urine every 15-20 minutes. The amount of urine passed can range from 3 litres in mild cases to up to 20 litres in severe cases.

Extreme thirst Excretion of an excessive amount of diluted urine.

Infants and young children who have diabetes insipidus may have the following signs and symptoms:

Unexplained fussiness or inconsolable crying Trouble sleeping Fever Vomiting Diarrhea Delayed growth Weight loss

TREATMENT

1. Desmopressin: It works just like natural AVP, stopping your kidneys producing urine when the level of water in body is low. The synthetic hormone will eliminate the increase in urination. Desmopressin can be taken as a nasal spray, in tablet form or as a form that melts in your mouth, between your gum and your lip. Desmopressin is very safe to use and has few side effects. However, possible side effects can include:

headache stomach pain feeling sick blocked or runny nose nosebleeds

Too much desmopressin or drink too much fluid while taking it, it can cause your body to retain too much water. This can result in:

dizziness feeling bloated hyponatraemia – a low level of sodium (salt) in your

blood.

2. Thiazide-diuretics: Thiazide diuretics can reduce the rate the kidney filters blood, which reduces the amount of urine passed from the body over time. Side effects are uncommon but include:

dizziness when standing indigestion very sensitive skin erectile dysfunction (impotence) in men

3. Non-steroidal anti-inflammatory drugs (NSAIDs):

such as ibuprofen, reduce urine volume, they're used

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in combination with thiazide diuretics. Long-term use of NSAIDs increase risk of stomach ulcer. DIABETES MELLITUS Diabetes mellitus (DM) is an endocrinological and/or metabolic disorder resulting from a defect in insulin secretion, insulin action, or both, characterized by the presence of chronic hyperglycemia by greater or

lesser impairment in the metabolism of carbohydrates, lipids and proteins. Diabetes mellitus is a disease of the pancreas, an organ behind your stomach that produces the hormone insulin. As the disease progresses tissue or vascular damage ensues leading to severe diabetic complications such as retinopathy, neuropathy, nephropathy, cardiovascular complications.

Figure 3: Causes of Diabetes mellitus CLASSIFICATION OF DIABETES MELLITUS: Diabetes mellitus is categorized into two major types- type 1 and type 2. The term type 1 and type 2 were widely used to describe IDDM (Insulin Dependent Diabetes Mellitus) and NIDDM (Non- Insulin Dependent Diabetes Mellitus), respectively. The term juvenile -onset diabetes has sometimes been used for IDDM and maturity-onset for NIDDM. Classification system identifies four types of diabetes mellitus: type 1, type 2, other specific types and gestational diabetes. Gestational Diabetes Mellitus (GDM)

Gestational diabetes mellitus is type of diabetes occurs in women who develop diabetes mellitus during gestation. Women who develop Type1 diabetes mellitus during pregnancy and women with undiagnosed asymptomatic Type 2 diabetes mellitus during pregnancy are classified with Gestational Diabetes Mellitus. Other specific type (Monogenic diabetes)

Types of diabetes mellitus of various known etiologies together form the classification called “Other Specific Types”. It includes persons with genetic defects of beta-cell function or with defects of insulin action; persons with diseases of the exocrine pancreas; or with pancreatic dysfunction caused by drugs, chemicals or infections.

Type 1 Diabetes: 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.

There is damage to beta cells from type 1 diabetes . Glucose doesn’t move into your cells because insulin isn’t there to do it. Instead it builds up in your blood and your cells starve. This causes high blood sugar. It is rare, only about 5% of people with diabetes have type 1. It affects men and women equally. Although the disease usually starts in people under 20, it can happen at any age. Three risk factors seem to be important in determining why a person develops type 1 diabetes:

inherited (or genetic) factors self-allergy (autoimmunity) environmental damage (e.g., from a virus or chemical)

1. Inheritance (genetic): People with type 1 diabetes

are more likely to have inherited certain cell types

(called HLA types). All people with type 1 diabetes

have an HLA type DR3 or DR4. It is determined by

using white blood cells (WBCs).

2. Self-allergy (autoimmunity): The allergic reaction is

against the cells in the pancreas (islet cells) that make

insulin. The presence of this in the blood is called an

antibody or “islet cell antibody” (ICA). Other diabetes

antibodies “GAD” antibodies, insulin auto-antibodies

can now be measured and also been found in the blood

of people who are developing diabetes. The antibodies

gradually disappear from the blood after the onset of

type 1 diabetes.

3. Environmental (virus or chemical): This factor may

be the bridge between the genetic part and the allergic

reaction.

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Figure 4: Type 1 diabetes causes due to insufficient insulin

SYMPTOMS: Heavy thirst Increased hunger (especially after eating) Dry mouth Nausea and vomiting Pain in your belly Frequent urination weight loss Fatigue Blurred vision Heavy, labored breathing Frequent infections of the skin, urinary tract, or

vagina. Signs of an emergency with type 1 diabetes include:

Shaking and confusion Rapid breathing Fruity smell to your breath Pain in your belly Loss of consciousness

TREATMENT

Insulin replacement therapy is the mainstay of treatment in patient with type 1 diabetes. Rapid-acting insulin may be given before, during, or immediately after a meal. Administration after a meal may help reduce the postprandial hyperglycemia associated with high fat meals. Insulin may be delivered with insulin syringes, insulin pens or external insulin pumps.

Conventional therapy– 2 daily injections of mixed insulin before breakfast and the evening meal.

Conventional therapy with a split night-time dose– 1 injection of mixed insulin before breakfast, 1 injection of rapid- or short-acting insulin before the evening meal and 1 injection of intermediate-acting insulin before the bedtime snack. This helps to reduce fasting hyperglycemia.

Medical Nutrition Therapy Dietary carbohydrate influences postprandial blood glucose levels the most and is the major determinant of meal-related insulin requirements.

Other medications: Pramlintide (Symlin): this medication given before

eating can slow the movement of food through stomach to curb the sharp increase in blood sugar that occurs after meals.

High blood pressure medications: Medications such as angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) also help keep kidneys healthy.

Cholesterol-lowering drugs

Investigational treatments: Pancreas transplant Islet cell transplantation Stem cell transplant

What Happens Without Treatment:

Retinopathy: This eye problem happens in about 80% of adults who have had type 1 diabetes.

Kidney damage: About 20% to 30% of people with type 1 diabetes get a condition called nephropathy. It can lead to other serious problems like kidney failure.

Poor blood circulation and nerve damage: Damaged nerves and hardened arteries lead to a loss of sensation in and a lack of blood supply to your feet. This raises your chances of injury and makes it harder for wounds to heal.

Type 2 Diabetes: Type 2 diabetes is caused by a combination of genetic factors related to impaired insulin secretion and insulin resistance and environmental factors such as obesity, overeating, lack of exercise, and stress, as well as aging. It is typically a multifactorial disease involving multiple genes and environmental factors to varying extents. The development of type 2 diabetes is clearly associated with a family history of diabetes. The three main risk factors for type 2 diabetes are: Overweight Insulin insensitivity Inheritance (genetics) Insulin insensitivity: Insulin does not work normally. People with type 2 diabetes may also have reduced insulin production. They will then need insulin shots. . This is different from type 1 diabetes, where insulin is not produce at all or is made in small amounts. Inheritance (genetics): Type 2 diabetes also has a strong genetic cause. People with type 2 diabetes do not have the same association with the HLA genes as do people with type 1 diabetes. They also do not make islet cell antibodies.

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Figure 5: Causes of Type 2 diabetes

SYMPTOMS Increased thirst and frequent urination Increased hunger Weight loss Fatigue Blurred vision Slow-healing wounds or frequent infections. Risk factors: Weight: It is a primary risk factor for type 2 diabetes.

The more fatty tissue, the more resistant cells become to insulin.

Inactivity: Physical activity helps to control weight, uses up glucose as energy and makes cells more sensitive to insulin.

Family history: The risk of type 2 diabetes increases if your parent or sibling has type 2 diabetes.

Race: Blacks, American Indians and Asian-Americans are more likely to develop type 2 diabetes than whites are.

Age: The risk of type 2 diabetes increases as you get older, especially after age 45. Type 2 diabetes is also increasing dramatically among children, adolescents and younger adults.

Prediabetes: Prediabetes is a condition in which your blood sugar level is higher than normal. If remains untreated, it often progresses to type 2 diabetes.

Gestational diabetes: Gestational diabetes during pregnancy, risk of developing type 2 diabetes increases.

Polycystic ovarian syndrome: For women, having polycystic ovarian syndrome increases the risk of diabetes.

Signs of trouble:

High blood sugar (hyperglycemia) Hyperglycemic hyperosmolar nonketotic

syndrome (HHNS) Increased ketones in your urine (diabetic

ketoacidosis) Low blood sugar (hypoglycemia)

TREATMENT: Glucose Lowering Therapy: Glucose-lowering oral agents may be effective with type 2 diabetes. The biguanide, metformin, is often the first oral agent used with teens.

Metformin is effective at reducing blood glucose levels without the risk of hypoglycemia.

Sulfonylureas-These medications help your body secrete more insulin.

Meglitinides-Stimulates the pancreas to secrete more insulin, they're faster acting, and the duration of their effect in the body is shorter.

These mainly have side effect like hypoglycaemia, which can be mild to moderate can cause fatal complication. The main adverse effects with thiazolidinediones are weight gain. To overcome these side-effects a new class of drugs called Gliptins or Dipeptidyl Peptidase 4 (DPP-4) inhibitors was introduced. These drugs work by prolonging the action of incretins which increase insulin levels. Gliptins act by two way which are as follows:

A. INCRETINS PROMOTE INSULIN SECRETION B. INHIBITION OF DPP-4 BOOSTS INCRETIN ACTION

Figure 6: Mechanism of Action of Incretins

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CLINICAL FEATURES OF DIABETES MELLITUS Type 1 diabetes mellitus

Symptoms include weight loss, polyurea, polydipsia, polyphagia, constipation fatigue, cramps, blurred vision, and candidiasis. Long lasting type 1 DM patients may susceptible to microvascular complications; and macrovascular disease.

Type 2 diabetes mellitus High risk of large vessel atherosclerosis commonly associated with hypertension, hyperlipidaemia and obesity. Most patients with type2 diabetes die from cardiovascular complications and end stage renal disease.

Table 1: Characteristics of Type 1&2 diabetes mellitus

PATHOGENESIS AND PATHOPHYSIOLOGY OF

DIABETES MELLITUS:

Type 1 diabetes mellitus: It is characterized by autoimmune destruction of insulin producing cells in the pancreas by CD4+ and CD8+ T cells and macrophages infiltrating the islets. Some features characterize type 1 diabetes mellitus as an autoimmune disease:

Presence of immuno-competent Presence of islet cell specific auto-antibodies Alterations of T cell mediated immune-regulation

Response to immunotherapy The auto-immune destruction of pancreatic β-cells, leads to a deficiency of insulin secretion which results in the metabolic changes associated with T1DM. The function of pancreatic α-cells is also abnormal and there is excessive secretion of glucagons in T1DM patients and glucagons secretion is not suppressed by hyperglycemia.

Deficiency of insulin leads to uncontrolled lipolysis and increase levels of free fatty acids in the plasma, which suppresses glucose metabolism in skeletal muscle.

Figure 7: Type 1 diabetes- glucose metabolism

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Type 2 diabetes mellitus: Two main pathological defects in type 2 diabetes: impaired insulin secretion through a dysfunction of the pancreatic β-cell, and impaired insulin action through insulin resistance. When insulin resistance predominates, the mass of β-cells undergoes a transformation which increases insulin supply. Thus plasma insulin concentration increases. “Relative” to the severity of insulin resistance, the plasma insulin concentration is insufficient to maintain normal glucose homeostasis.

Insulin resistance and hyperinsulinemia eventually lead to impaired glucose tolerance. Insulin resistance: Resistance to the action of insulin will result in- impaired insulin mediated glucose uptake by muscle and fat, incomplete suppression of hepatic glucose output and impaired triglyceride uptake by fat. To overcome the insulin resistance, islet cells will increase the amount of insulin secreted. Endogenous glucose production is accelerated in patients with type 2 diabetes.

Figure 8: Type 2 diabetes- glucose metabolism COMPLICATIONS OF DIABETES MELLITUS 1- Acute complications

Hypoglycemia Hyperglycemic crises Diabetes Ketoacidosis (DKA) Hyperglycemic hyperosmolar state (HHS)

2- Chronic complications: Micro vascular complications Diabetic retinopathy Diabetic nephropathy Diabetic neuropathy Macrovascular disease

3- Other complications and associated conditions Impaired growth and development Associated autoimmune conditions Hypothyroidism Hyperthyroidism Celiac disease Vitiligo Primary adrenal insufficiency (Addison’s disease) Lipodystrophy Necrobiosis lipoidica diabeticorum Non-alcoholic fatty liver disease Infections seen in patients with diabetes Limited joint mobility Edema

DIAGNOSIS OF DIABETES MELLITUS

A number of laboratory tests can confirm the diagnosis of diabetes. Finger stick blood glucose: It is easy to perform, and

the result is available quickly. The test involves

sticking the patient's finger for a blood sample, which is then placed on a strip that has been inserted into a machine that reads the blood sugar level. These machines are only accurate to within about 10%-20% of true laboratory values.

Fasting plasma glucose: The patient will be asked not to eat or drink for eight hours before having blood drawn. If the blood glucose level is greater than or equal to 126 mg/dL, they probably have diabetes.

If the result is abnormal, the fasting plasma glucose test may be repeated on a different day to confirm the result. Or the patient may undergo an oral glucose tolerance test.

If fasting plasma glucose level is greater than 100 but less than 126 mg/dL, then the patient is considered to be Prediabetes. They are at high risk of developing diabetes.

Oral glucose tolerance test: This test involves drawing blood for a fasting plasma glucose test, then drawing blood for a second glucose test at two hours after drinking a specific sweet drink.

If the blood sugar level after the sugar drink rises over or equal to 200 mg/dL, the patient has diabetes.

If the blood glucose level is between 140 and 199 mg/dL, then the patient has impaired glucose tolerance (IGT), also a prediabetic condition.

Glycosylated hemoglobin or hemoglobin A1c: This test measures how high the blood sugar levels have lasts for 120 days. The hemoglobin A1c test is the best measurement of blood sugar control in people known to have diabetes. Hemoglobin A1c levels of 7% or less indicate good glucose control. 8% or higher indicates that blood sugar levels are too high.

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PSYCHOLOGICAL ASPECTS OF DIABETES

MANAGEMENT

Diabetes is considered as one of the most emotionally and behaviorally demanding chronic illnesses. Psychosocial adaptation is an important outcome, of both quality of life and the effectiveness of treatment. Patients in poor psychological health cannot cope up with the motivation and emotional strength to self-manage their diabetes. Adaptation starts with the diagnosis, to which every patient respond differently. It may come as a shock, and can induce emotional distress in patients. Some patients initially react with indifference, or even relief, on discovering that it was ‘only’ diabetes that caused their physical complaints. The major physical and psychosocial concern is increase number of overweight children and young adults developing type 2 diabetes. To prevent diabetes related complications- active, problem-focused, proactive coping behaviors are required. Patients must care for the daily management of the disease. The greatest problem is of diabetic ketoacidosis (DKA), which is more during adolescence; it is not a physiological subtype but is caused by failure to take insulin. It affects adolescent from lack of parental involvement in the diabetes care. It is needed to clarify whether the problem is related to denial, fear of social stigma, weight gain or fear of ‘hypos’. Psychological problems: The most common is Non-adherence. It is behaviour in a patient who has balanced the pros and cons of intensive self-management. Poor diabetes control is more common in: • Adolescents • Adults of lower socioeconomic status • Women • Patients with depression or an eating disorder (anorexia, bulimia, binge-eating).

Depression is most common in those with diabetes compared with the general population, and is associated with hyperglycaemia. Insulin-treated patients with less awareness of hypoglycaemic symptoms are at risk of developing fear of this. Management of psychological problems: This requires a better approach to diabetes, and open communication between patient and health care providers regarding psychological problems. Many different approaches have been considered are as follows:

Undertake a multidisciplinary assessment, including a psychosocial perspective.

Less intensive insulin regimens may be used temporarily. Use or develop therapeutic group programmes for young

people with diabetes.

FIVE INNOVATIVE NEW PRODUCTS FOR DIABETES:

The FDA recently approved several new drugs along with a novel device that can replace fingersticks and an “artificial pancreas” for patients with diabetes.

1. The G5 Mobile Continuous Glucose Monitoring System:

The G5 Mobile Continuous Glucose Monitoring System, made by Dexcom, can replace finger stick blood glucose testing for diabetics. This is the first FDA-approved continuous glucose monitoring system that can be used for diabetes treatment without confirmation with finger stick test. The G5 Mobile Continuous Glucose Monitoring System uses a small sensor wire inserted just below the skin that continuously measures and monitors glucose levels. Real-time results are sent wirelessly every five minutes to a dedicated receiver and a compatible mobile device running a mobile app. Then, alarms and alerts indicate glucose levels above or below user-set thresholds.

Figure 9: The G5 Mobile Continuous Glucose Monitoring System

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The Dexcom G5 has not been tested during MRI or CT scans or with diathermy treatment. The magnetic fields and heat could damage the components of the Dexcom G5, which might cause it to display inaccurate blood glucose readings or fail to provide alerts. Taking medications with acetaminophen while wearing the Dexcom G5 may falsely raise the glucose readings. The level of inaccuracy depends on the amount of acetaminophen active in your body.

2. Synjardy XR:

It is a combination of two antihyperglycemic drugs: empagliflozin and metformin hydrochloride extended-release tablets (Synjardy XR), made by Boehringer Ingelheim and Eli Lilly. It makes blood

glucose control easier for patients with type 2 diabetes. Empagliflozin is an orally-active inhibitor of the sodium-glucose co-transporter 2. SYNJARDY XR tablets for oral administration are available in four dosage strengths containing: 5 mg empagliflozin and 1000 mg metformin hydrochloride extended-release 10 mg empagliflozin and 1000 mg metformin hydrochloride extended-release 12.5 mg empagliflozin and 1000 mg metformin hydrochloride extended-release 25 mg empagliflozin and 1000 mg metformin hydrochloride extended-release

Figure 10: Synjardy XR

3. Xultophy 100/3.6:

Made by Novo Nordisk. Xultophy, a combination of Tresiba (insulin degludec injection) and Victoza (liraglutide) injection, is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. The drug is administered as a once-daily injection from a prefilled pen, and can be taken with

or without food. It is supplied as an injection for subcutaneous administration in thigh, upper arm or abdomen. It is contraindicated in patients with or family history of medullary thyroid carcinoma or in patients with Multiple Endocrine Neoplasia syndrome type 2.

Figure 11: Xultophy 100/3.6

4. Soliqua 100/33:

Soliqua 100/33 contains a combination of insulin glargine and lixisenatide. Insulin glargine is long-acting insulin that starts to work several hours. Lixisenatide is a diabetes medicine that helps pancreas to produce insulin more efficiently. SOLIQUA 100/33 may cause serious side effects, including:

Serious allergic reactions: Symptoms may include swelling of your face, problems breathing or swallowing, severe rash or itching, fainting or feeling dizzy, and very rapid heartbeat.

Low blood sugar (hypoglycemia) Kidney problems (kidney failure). Low potassium in your blood (hypokalemia). Heart failure

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Figure 12: Soliqua 100/33

5. Medtronic’s MiniMed 670G hybrid:

The first “artificial pancreas,” a device to automatically monitor glucose and provide appropriate basal insulin doses for patients with type 1 diabetes. The device, Medtronic's MiniMed 670G hybrid closed loop system, is made up of an insulin pump and continuous glucose monitor (CGM). This is the first such machine in the world with that level of automation, and thus it is informally being called the first "artificial pancreas" system.

It measures the user’s glucose levels for up to seven days, an insulin pump that delivers insulin to the user, and a glucose meter used to calibrate the CGM. It is able to decrease or stop insulin delivery when user’s glucose is low, or increase the insulin delivery when glucose levels are high with no input from the user. The glucose sensor contains a wire that is inserted under the skin on the abdomen and measures glucose values in the tissue fluid. Patients should always remove their pump, sensor, transmitter, and meter before entering a room that has x-ray, MRI, diathermy, or CT scan equipment.

Figure 13: Medtronic’s MiniMed 670G hybrid

CONCLUSION Diabetes is a condition in which pancreas do not function properly. DI is characterized by polyuria and polydipsia and inappropriate secretion ADH. DM is a metabolic disorder: lack in insulin secretion characterized by the presence of chronic hyperglycemia. It is considered as one of the most emotionally and behaviorally demanding chronic illnesses (Psychological Problem). The greatest problem is of diabetic ketoacidosis (DKA), which is more during adolescence. To cope up with it daily management (proper medications and psychological) is required.

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