1. DIABETES MELLITUS, IT’S MANAGEMENT AND INSULIN, IT’S MANAGEMENT
BY :
ELAINE P. JAVIER

2. DIABETES = a condition in which there’s too many excretion of urine and can be caused by a lack of hormone called antidiuretic or ADH that limits the amount of urine made as in Diabetes Insipidus or it can also result from a higher blood sugar level as in Diabetes Mellitus.

3. DIFFERENT KINDS OF DIABETES:
1) Diabetes Insipidus = decrease of anti-diuretic hormone
2) Syndrome of Inappropriate Anti-diuretic Hormone. Secretion ( SIADH ) = increase of anti-diuretic hormone resulting in water intoxication.
3) Diabetes Mellitus = chronic disorder of carbohydrates, protein and fat metabolism characterized by an imbalance between the insulin supply and demand.

4. Diabetes mellitus , often referred to simply as diabetes , pass through urine, is a syndrome of disordered metabolism, usually due to a combination of hereditary and environmental causes, resulting in abnormally high blood sugar levels (hyperglycemia). Blood glucose levels are controlled by the hormone insulin made in the beta cells of the pancreas. Diabetes and its treatments can cause many complications and may occur if the disease is not adequately controlled.

5. DIFFERENT TYPES OF DIABETES MELLITUS a) D M Type 1 = Insulin Dependent Diabetes Mellitus (IDDM ) b) D M Type 11 = Non-Insulin Dependent Diabetes (NIDD ) c) D M Type 111= Gestational Diabetes

6. Diabetes Mellitus Type 1
Diabetes mellitus type 1 Type 1 diabetes ( formerly known as "childhood", "juvenile" or "insulin-dependent" diabetes) or juvenile diabetes) is a form of diabetes mellitus. Type 1 diabetes is an autoimmune disease that results in destruction of insulin-producing beta cells of the pancreas. Glycosuria or glucose in the urine causes the patients to urinate more frequently, and drink more than normal (polydipsia). Type 1 has been lethal unless treatment with exogenous insulin, usually via injections which replaces the missing hormone formerly produced by the now non-functional beta cells in the pancreas.

7. Pathophysiology of D. M. Type 1:
Virally triggered Autoimmune Response
Immune System’s attack on virus Infected cells
Directed against the beta cells in the pancreas
Infection of a virus
Ex. Coxsackie virus, German measles
Pancreatic Beta Cells in the Islets of Langerhans are destroyed or damaged sufficiently thus abolish endogenous Insulin production.

8. Signs and Symptoms: Kussmaul breathing ( outstanding sign )
Polydipsia = too much thirst
Polyphagia = too much eating
Polyuria = too much urination
Hypoglycemia or Hypergycemia
Weakness and warm skin
Emotionally lability
Abdominal discomfort
Ketoacidosis
Muscle cramps
Irritability
Nausea
Glycosuria
Weight loss
Anxiety attacks
Loss of Na and K
Ketonuria

9. Diagnosis : 1) C-peptide Assay = The most definite laboratory test to distinguish Type 1 from Type 2 diabetes , which is a measure of endogenous insulin production since external insulin has included C-peptide. 2) Glutamic Acid Decarboxylase 65 Antibodies = has been proposed as an improved test for differentiating between Type 1 and Type 2 diabetes as it appears that the immune system malfunction is connected with their presence. 3) Glucose Tolerance Test = a test of the body’s ability to process carbohydrate by giving a dose of glucose and then measuring the blood and urine for glucose. ( blood drawn then drink concentrated glucose solution then blood drawn again ). ORAL BASELINE FASTING – 70 TO minutes fasting = 110 to 170 mg/dL 60 minutes fasting ( 1 hr ) = 120 to 170 mg/dL 90 minutes fasting = 100 to 140 mg/dL 120 minutes fasting (2 hrs) = 70 to 120 mg/dL 4) Hemoglobin A1C = glycocylate hemoglobin value is the most accurate diagnostic tool in determining the current glucose within 60 to 100 days. It asses blood glucose control prior to the current status. a. 5 to 8 % -- mild, good control b. 9 % -- fair control c. Above 10 % -- poor control

10. Laboratories :
Blood glucose = normal is 70 to 110 mg/dL
Electrolytes
Venous pH
Urine analysis for glucose and ketones
Hemoglobin A1C level
C-peptide insuin level
Islet-cell antibodies
T4 and thyroid antibodies

11. Acute complications: 1) Diabetic ketoacidosis
Diabetic ketoacidosis (DKA) is an acute and dangerous complication that is always a medical emergency. no insulin levels cause the liver to turn to fat for fuel On presentation at hospital, the patient in DKA is typically dehydrated, and breathing rapidly and deeply. Abdominal pain is common and may be severe. The level of consciousness is typically normal until late in the process, when lethargy may progress to coma. Ketoacidosis can easily become severe enough to cause hypotension, shock, and death. Ketoacidosis is much more common in type 1 diabetes than type 2. Hyperglycemia,
Signs and Symptoms of DKA:
Dull headache – warning sign
Dehydration – 1st sign of DKA
Ketonemia/ketonuria
Kussmaul breathing
Polydipsia , Polyuria
Fatigue
Dry lips
Nausea
Sunken eyes , blurred vision
Pain below the breastbone
Temperature rises and falls
Acetone or fruity breath odor
Metabolic Acidosis
Acute complications:

12. 2) Hypoglycemia Hypoglycemia, or abnormally low blood glucose, is an acute complication of several diabetes treatments. It is rare otherwise, either in diabetic or non-diabetic patients. The patient may become agitated, sweaty, and have many symptoms of sympathetic activation of the autonomic nervous system resulting in feelings akin to dread and immobilized panic. In most cases, hypoglycemia is treated with sugary drinks or food. In severe cases, an injection of glucagon (a hormone with the opposite effects of insulin) or an intravenous infusion of dextrose D50/50 via fast drip (microset) is used for treatment, but usually only if the person is unconscious. 3) Diabetic coma – deep unconsciousness leading to death

13. Treatment:
Type 1 is treated with insulin replacement therapy — usually by injection or insulin pump, along with attention to dietary management, typically including carbohydrate tracking, and careful monitoring of blood glucose levels using Glucose meters.
Untreated Type 1 diabetes can lead to one form of diabetic coma, diabetic ketoacidosis, which can be fatal. At present, insulin treatment must be continued for life; this may change when better treatment, or a cure, becomes clinically available. Continuous glucose monitors have been developed which can alert patients to the presence of danger.
Insulin
Pancreas Transplantation through surgery
Islet Cell Transplantation

15. Gene therapy approach:

16. "Immunization" Approach: A substance designed to cause lymphocyte cells to cease attacking beta cells, DiaPep277 is a peptide fragment of a larger protein called HSP60. Given as a subcutaneous injection Intra-nasal insulin: There is pre-clinical evidence that a Th1-Th2 shift can be induced by administration of insulin directly onto the immune tissue in the nasal cavity. Diamyd Diamyd is the name of a vaccine being developed by Diamyd Medical. Injections with GAD65, an autoantigen involved in type 1 diabetes.

17. Diabetes Mellitus Type 2
Type 2 diabetes mellitus is characterized differently due to insulin resistance or reduced insulin sensitivity, combined with reduced insulin secretion. The defective responsiveness of body tissues to insulin almost certainly involves the insulin receptor in cell membranes. At this stage hyperglycemia can be reversed by a variety of measures and medications that improve insulin sensitivity or reduce glucose production by the liver. As the disease progresses the impairment of insulin secretion worsens, and therapeutic replacement of insulin often becomes necessary and is usually seen in adult.

18. Signs and Symptoms: Poydipsia Polyphagia Polyuria Hyperglycemia
Hyperosmolar
Glycosuria
Chronic fatigue
Weakness
Paresthesia
Skin infection

19. Oral Glucose Tolerance Test
Laboratories :
Fasting Blood Sugar = normal is 70 to 110 mg/100 mL or to mmol/L
Oral Glucose Tolerance Test
Random Plasma Glucose = normal > 200 mg/d/L
Fasting Plasma Glucose = normal > 126 mg/dL, then will be given oral glucose with 75 g glucose load , after 2 hours, blood sugar will go up. On the 3rd hour, it will go to back to normal.
Hemoglobin A1C = glycocylate hemoglobin value, usually a measurement of blood glucose for the past 3 months.
a. 5 to 8 % -- mild, good control
b. 9 % -- fair control
c. Above 10 % -- poor control

20. Chronic complications: 1) Nonketotic hyperosmolar coma Hyperosmolar nonketotic state (HNS) or Hyperosmolar Hyperglycenia State ( HHS) is an acute complication sharing many symptoms with DKA, but an entirely different origin and different treatment. A person with very high 600 and above mmol/dl blood glucose levels, water is osmotically drawn out of cells into the blood and the kidneys eventually begin to dump glucose into the urine. This results in loss of water and an increase in blood osmolarity. If fluid is not replaced (by mouth or intravenously), the osmotic effect of high glucose levels, combined with the loss of water, will eventually lead to dehydration. The body's cells become progressively dehydrated as water is taken from them and excreted. Electrolyte imbalances are also common and are always dangerous. As with DKA, urgent medical treatment is necessary, commonly beginning with fluid volume replacement. Lethargy may ultimately progress to a coma, though this is more common in type 2 diabetes than type 1.

21. 2) Vascular disease Chronic elevation of blood glucose level leads to damage of blood vessels (angiopathy). The endothelial cells lining the blood vessels take in more glucose than normal. They then form more surface glycoproteins than normal, and cause the basement membrane to grow thicker and weaker. In diabetes, the resulting problems are grouped under "microvascular disease" (due to damage to small blood vessels) and "macrovascular disease" (due to damage to the arteries).

22. Image of fundus showing scatter laser surgery for diabetic retinopathy

23. The damage to small blood vessels leads to a microangiopathy, which can cause one or more of the following:
Diabetic retinopathy, growth of friable and poor-quality new blood vessels in the retina as well as macular edema (swelling of the macula), which can lead to severe vision loss or blindness.
Diabetic neuropathy, abnormal and decreased sensation, usually in a 'glove and stocking' distribution starting with the feet but potentially in other nerves, later often fingers and hands. When combined with damaged blood vessels this can lead to diabetic foot (see below). Diabetic amyotrophy is muscle weakness due to neuropathy.
Diabetic nephropathy, damage to the kidney which can lead to chronic renal failure, eventually requiring dialysis.
Diabetic cardiomyopathy, damage to the heart, leading to diastolic dysfunction and eventually heart failure.

24. 2) Macrovascular disease leads to cardiovascular disease, to which accelerated atherosclerosis is a contributor:
Coronary artery disease, leading to angina or myocardial infarction ("heart attack")
Stroke (mainly the ischemic type)
Peripheral vascular disease, which contributes to intermittent claudication (exertion-related leg and foot pain) as well as diabetic foot.
Diabetic myonecrosis ('muscle wasting') Diabetic foot, often due to a combination of sensory neuropathy (numbness or insensitivity) and vascular damage, increase rates of skin ulcers and infection and, in serious cases, necrosis and gangrene.
Carotid artery stenosis does not occur more often in diabetes, and there appears to be a lower prevalence of abdominal aortic aneurysm.
Diabetic encephalopathy is the increased cognitive decline and risk of dementia observed in diabetes. Various mechanisms are proposed, including alterations to the vascular supply of the brain and the interaction of insulin with the brain itself.

25. HYPERGLYCEMIA: 3 P’s HYPOGLYCEMIA: Cold and Clamy to touch
Polyuria = too much urination
Polydyspsia = too much thirst
Polyphagia = too much eating
HYPOGLYCEMIA:
Cold and Clamy to touch
Early sign is tremulousness
Confusion
Headache
Extreme fatigue
Shakiness, Sweating
Tremor , Tachycardia,
Tingling sensation around the mouth
Diaphoresis
Restlessness
Irritability
Pallor
Seizure

26. S/S DKA HHS Plasma Glucose Serum Na Potassium Bicabonate Ketones
Fruity/Aceton breath
odor pH
Serum Osmolality
Menthol states
Dehydration
Prognosis
DKA
300 to 600 mg/dl
Low/normal
H/L or normal
Low
Present
Below 320 mOsm/kg
Mental Status Changed
Mild to moderate
< 10% mortality
HHS
Above 600 mg/dl
High/Normal
H/normal
High
Absent
Norma;
Above 320 mOsm/kg
Mental Status Changed
SEVERE
15% mortality

27. Management of Diabetes Mellitus:
Diet = 50 to 60 % of carbohydrates , 20 to 30 % Fats, to 20 of cholesterol
Insulin
Antidiuretic Agents
Blood sugar monitoring
Exercise
Transplant of pancreas or insulin
Ensure adequate food intake
Scrupulous foot care

28. GESTATIONAL DIABETES :
Gestational Diabetes Mellitus (GDM) resembles type 2 diabetes in several respects, involving a combination of relatively inadequate insulin secretion and responsiveness. It occurs in about 2%–5% of all pregnancies and may improve or disappear after delivery. Gestational diabetes is fully treatable but requires careful medical supervision throughout the pregnancy. About 20%–50% of affected women develop type  2 diabetes later in life.
Risks to the baby include macrosomia (high birth weight), congenital cardiac and central nervous system anomalies, and skeletal muscle malformations. Increased fetal insulin may inhibit fetal surfactant production and cause respiratory distress syndrome. Hyperbilirubinemia may result from red blood cell destruction. In severe cases, perinatal death may occur, most commonly as a result of poor placental profusion due to vascular impairment. Induction may be indicated with decreased placental function. A cesarean section may be performed.

29. Signs and Symptoms: Polydipsia Polyphagia Polyuria Weight loss Fatigue Nuasea and vomiting = common symptoms

30. Laboratory Data : Elevated FBS usually on the 2nd & 3rd trimster , GTT Treatment and Management High protein diet Exercise is squatting Monitor blood glucose leves Allow calcium 300 mg/day Ist Trimester has decrease need of insulin 2nd Trimester has increase demand of insulin Use only Regular and NPH: A.M. dose is 2:1 / P.M. dose is 1:1. Signs & Symptoms of Hypoglycemic New Born: Jittery , Tremors Irritability , Irregular respiration Letargic Shaky

31. I N S U L I N:

32. WHAT IS INSULIN ?
Insulin is a hormone. And like many hormones, insulin is a protein.   Insulin is secreted by groups of cells within the pancreas called islet cells. The pancreas is an organ that sits behind the stomach and has many functions in addition to insulin production. Carbohydrates (or sugars) are absorbed from the intestines into the bloodstream after a meal. Insulin is then secreted by the pancreas in response to this detected increase in blood sugar.

33. Where Does Commercial Insulin Come From
Where Does Commercial Insulin Come From? The first successful insulin preparations came from cows (and later pigs). The bovine (cow) and porcine (pig) insulin worked very well for the vast majority of patients, but some could develop an allergy or other types of reactions to the foreign protein. In the 1980's technology had advanced to the point where we could make human insulin. The advantage would be that human insulin would have a much lower chance of inducing a reaction because it is not a foreign protein.

34. Normal Regulation of Blood Glucose

35. Many Type 1 treatments include combination use of regular or NPH insulin, and/or synthetic insulin analogs (eg, Humalog, Novolog or Apidra) in combinations such as Lantus/Levemir and Humalog, Novolog or Apidra. Another treatment option is the use of the insulin pump (eg, from Deltec Cozmo, Animas, Medtronic Minimed, Insulet Omnipod, or ACCU-CHEK). A blood lancet is used to pierce the skin (typically of a finger), in order to draw blood to test it for sugar levels.

36. There are several problems with insulin as a clinical treatment for diabetes:
Mode of administration.
Selecting the 'right' dose and timing.
Selecting an appropriate insulin preparation (typically on 'speed of onset and duration of action' grounds).
Adjusting dosage and timing to fit food intake timing, amounts, and types.
Adjusting dosage and timing to fit exercise undertaken.
It is dangerous in case of mistake (most especially 'too much' insulin).

37. The commonly used types of insulin are:
Rapid-acting types are presently insulin analogs, such as the insulin analogs aspart or lispro. these begin to work within 5 to 15 minutes and are active for 3 to 4 hours. Most insulins form "clumps" which delay entry into the blood in active form.
Short-acting, such as regular insulin – starts working within 30 minutes and is active about 5 to 8 hours.
Intermediate-acting, such as NPH, or semilente insulin – starts working in 1 to 3 hours and is active 16 to 24 hours.
Long-acting, such as ultralente insulin – starts working in 4 to 6 hours, and is active well beyond 32 hours.
Insulin glargine and Insulin detemir – both insulin analogs which start working within 1 to 2 hours and continue to be active, without major peaks or dips, for about 24 hours, although this varies in many individuals.
A mixture of NPH and regular insulin – starts working in 30 minutes and is active 16 to 24 hours. There are several variations with different proportions of the mixed insulins.
A mixture of Semilente and Ultralente (typically in the proportion 30% Semilente to 70% Ultralente), known as Lente, is typically active for an entire 24 hour period. Beef Lente, in particular, has a very 'flat' profile.

38. Modes of administration
Unlike many medicines, insulin cannot be taken orally. Like nearly all other proteins introduced into the gastrointestinal tract, it is reduced to fragments (even single amino acid components),
Subcutaneous
Insulin is usually taken as subcutaneous injections by single-use syringes with needles, an insulin pump, or by repeated-use insulin pens with needles.
Insulin pump:
Insulin pumps are a reasonable solution. Advantages to the patient are better control over background or 'basal' insulin dosage, bolus doses calculated to fractions of a unit, and calculators in the pump that may help with determining 'bolus' infusion dosages.
Inhalation
In 2006 the U.S. Food and Drug Administration approved the use of Exubera, the first inhalable insulin

39. Injection Site Selection
The most common injection site is the abdomen (or stomach). The back of the upper arms, the upper buttocks or hips, and the outer side of the thighs are also used. These sites are the best to inject into for two reasons:
They have a layer of fat just below the skin to absorb the insulin, but not many nerves - which means that injecting there will be more comfortable than injecting in other parts of your body.
They make it easier to inject into the subcutaneous tissue, where insulin injection is recommended.

41. Rotating Your Injection Sites
If you inject insulin three or more times a day then it’s a good idea to rotate your injection sites. Injecting in the same place much of the time can cause hard lumps or extra fat deposits to develop. These lumps are not only unsightly; they can also change the way insulin is absorbed, making it more difficult to keep your blood glucose on target.
Follow these two rules for proper site rotation:
Same general location at the same time each day.
Rotate within each injection site.

42. Most insulin enters the blood:
  Most insulin enters the blood:
Fastest from the abdomen (stomach)
A little slower from the arms
Even slower from the legs
Slowest from the buttocks

43. COMPLICATIONS OF INSULIN:
SOMOGYI PHENOMENON EFFECTS (Sa Gabi) = rebound hypoglycemia during the night until morning ; Reduced or adjust insulin and give snack.
INSULIN WANING (In bed Time until inumaga) = hyperglycemia from bedtime until morning ; Increase NPH dose in the evening.
Dawn Phenomenon = hyperglycemia at dawn due to too early administration of insulin; Delay the insulin in the evening dose .

44. The End...