Diabetes Mellitus Fifth Stage-Medicine

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Diabetes MellitusFifth Stage-Medicine

• Dr. Sarbast Fakhradin
• MBChB, MSc Diabetes Care Management

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Comprehensive diabetes care of type 2 DM
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• Patient education follow up DAFNE DESMOND
• It is essential that people with diabetes
  understand their disorder and learn to handle all
  aspects of their management educating patients
  about diabetes complications.
• Carry a diabetic card stating their name and
  address.
• Driving

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• Patient education follow up DAFNE DESMOND
• Blood glucose monitoring
• Target Preprandial capillary plasma glucose
  (70-130 mg/dl)
• Target postprandial capillary plasma glucose (lt
  180 mg/dl)
• A. Treatment with insulin
• Regular BG monitoring should be performed by all
  patients to adjust the insulin dose and detect
  hypoglycaemia
• Daily pre-prandial and bedtime measurements are
  usually recommended

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• Treatment with oral hypoglycemic agents
• BG monitoring is optional in many patients with
  stable type 2 diabetes.
• Monitoring is most useful in patients taking
  sulphonylureas, during intercurrent illness and
  prescription of corticosteroids, and during
  changes in therapy.
• Lower limbs feet
• Blood pressure lt 130/80
• Smoking alcohol
• Hypoglycemic episodes.
• Psychological support
• Target Lipid profile Cholesterollt 200mg/dl,
• LDL lt 100
  mg/dl,
• TG lt 150
  mg/dl
• HDLgt 40
  mg/dl.

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Lifestyle modification

• 1. Healthy diet
• 2. Regular Exercise in the form of walking,
  gardening, swimming or cycling, approximately 30
  minutes daily, as this improves insulin
  sensitivity and the lipid profile and lowers
  blood pressure.
• 3. Stop smoking
• 4. Reduce/stop alcohol intake
• 5. Salt reduce sodium intake to no more than 6
  g daily.

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• The glycaemic index (GI) of a carbohydrate-contain
  ing food is a measure of the change in blood
  glucose following its ingestion. Consumption of
  foods with a low GI is encouraged.
• All the CHO prescribed should be taken in the
  form of starches and other complex sugars.
• Fiber- rich foods (e.g barley, oats, legumes,
  beans lentils) has been associated with
  improved blood glucose control lower blood
  lipids in both normal, diabetic hyperlipidemic
  persons.
• Low-calorie and sugar-free drinks are useful for
  patients with diabetes. These drinks usually
  contain non-nutritive sweeteners. Many 'diabetic
  foods' contain sorbitol, are expensive and high
  in calories, and may cause gastrointestinal
  side-effects. As a result, these foods are not
  recommended as part of the diabetic diet.

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• Recommended composition of diet for people with
  diabetes
• CHO 40-65
• Fat lt 35 ( saturated lt10)
• Protein 10-15
• Fruit/Vegetable 5 portions daily

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Anti-Diabetic Medications

• Oral Agents
• 1. Biguanides (Metformin)
• 2. Insulin Secretagogues Sulphonylureas
  (Gliclazide)
• 3.Insulin Secretagogues Non-sulphonylureas
  (Repaglinide)
• 4. DPP4 inhibitor (Sitagliptin)
• 5. a-glucosidase inhibitors (Acarbose)
• 6. Thiazolidinediones (TZDs) (Pioglitazone)
• Injections
• 1. Insulin
• 2. GLP-1 agonist (Incretin mimetic) Exenatide
  Liraglutide

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Biguanides (Metformin)

• First drug of choice for obese patients in
  whom strict dieting has failed to control type 2
  diabetes.
• Insulin sensitivity and peripheral glucose uptake
  are increased,
• Impairs glucose absorption by the gut and
  inhibits hepatic gluconeogenesis
• It does not increase insulin secretion and seldom
  causes hypoglycaemia.
• Metformin is given with food.

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Biguanides (Metformin)

• Glucose-lowering effect of metformin is
  synergistic with that of sulphonylureas.
• Improves lipid profiles reduces risk of CA.
• SE Dyspepsia, Risk of lactic acidosis
  contraindicated in patients with impaired renal
  or hepatic function, drinking alcohol in excess,
  hypoxia, shock.
• Not contraindicated in pregnancy.

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SULPHONYLUREAS

• Mainly for people with type 2 diabetes who are
  not overly obese.
• First Generation Tolbutamide (well tolerated,
  short acting, useful in elderly), Chlorpropamide
  Very long acting (up to 60 hours), avoid in
  elderly.
• Second generation Glibenclamide, Gliclazide,
  Glimepiride, Glipizide.
• Glibenclamide is prone to induce severe
  hypoglycaemia (avoid in the elderly)
• Principally stimulate production of insulin, may
  reduce glucagon levels.

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SULPHONYLUREAS

• SUs can cause hypoglycaemia and their use should
  therefore be closely monitored in the elderly
  in those with nephropathy.
• Several drugs can potentiate their hypoglycaemic
  effect (e.g. salicylates, phenylbutazone and
  antifungal agents)
• SE Hypoglycemia, increased appetite and weight
  gain, skin rashes (hypersensitivity) and G.I.
  Disturbances, cholestatic Jaundice, blood
  dyscrasia. Feature of disulfiram- like reaction
  occur in some patients after taking alcohol.
• Occasionally chlorpropamide can induce (SIADH).

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Meglitinides - prandial glucose regulators

• Repaglinide, Nateglinide
• Stimulates insulin release (rapid and short
  acting)
• Better control of postprandial hyperglycaemia
• Take before meals.
• It is less likely to cause hypoglycaemia than
  sulphonylureas.

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Alpha-glucosidase inhibitors (Acarbose)

• Carbohydrate digestion in the small intestine is
  slowed down by selectively inhibiting
  disaccharidases
• Glucose is not absorbed into the bloodstream so
  quickly.
• SE Bloating, flatulence, diarrhoea and abdominal
  pain, especially upon initial treatment.

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Thiazolidinediones (pioglitazone)

• Bind and activate peroxisome proliferator-activate
  d receptor-? (PPAR? agonists).
• Reduced insulin resistance and decreased insulin
  levels
• insulin concentrations are not increased
  hypoglycemia is not a problem.
• Fat redistribute from the abdominal stores and
  into subcutaneous depots. However, body weight
  and total body fat are increased.
• Pioglitazone may reduce myocardial infarctions
  and strokes (improvement in endothelial
  function), but increase the risk of HF?

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Thiazolidinediones (pioglitazone)

• SE sodium and fluid retention, which is
  aggravated if they are combined with insulin,
  upper limb fractures.
• TZDs must be avoided in patients with cardiac
  failure, hepatic impairment or severe renal
  insufficiency.
• Increase LDL (non-atherogenic form?), increased
  HDL, lowered FFA, lowered triglycerides.

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Oral hypoglycaemics
Biguanides
Thiazolidinediones
? Insulin resistance
? Glucose output ? Insulin resistance
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Mechanisms of glucose-stimulated insulin secretion
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• Incretin-based therapies
• The secretion of insulin in response to a rise in
  blood glucose is greater when glucose is given by
  mouth than by intravenous infusion. In part this
  is caused by secretion of gut hormones, or
  incretins (Glucagon-like peptide (GLP-1), which
  potentiate glucose-induced insulin secretion.
• GLP-1 suppresses glucagon secretion, delays
  gastric emptying, reduces appetite and encourages
  weight loss.

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• Incretin-based therapies (Cont.)
• They improve postprandial glucose excursions and
  early satiety
• GLP-1 is rapidly degraded by the enzyme,
  dipeptidyl peptidase 4, inhibitors of this enzyme
  can be used to prolong its biological effect.
• The DPP-4 inhibitors or gliptins (sitagliptin,
  vildagliptin and saxagliptin) are oral agents
  which act in this manner.

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• Incretin-based therapies (Cont.)
• Exenatide Liraglutide (SC injection) are
  Synthetic GLP-1 receptor antagonists with longer
  therapeutic action. They induce weight loss in
  most patients. SE pancreatitis GI disturbance.
• Incretin-based therapies are most useful in obese
  patients and can be used in combination with
  other oral anti-diabetic agents.

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Insulin

• Insulin are either bovine or porcine, human
  insulin produced by recombinant DNA technology
  protein engineering technique.
• In most countries, the insulin concentration in
  available formulations has been standardised at
  100 U/mL.
• Plastic Syringe or pen injector.
• Insulin is usually given by the SC route, IV or
  IM routes.
• Rotation of injection sites is recommended to
  reduce insulin injection site damage.

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Insulin (Cont.)

• It is removed mainly by the liver and also the
  kidneys plasma insulin concentrations are
  elevated in patients with liver disease or renal
  failure.
• Absorption from the abdomen is faster than from
  thighs or upper arms and may be preferred for
  short- acting preparation.
• Insulin absorption may be influenced by insulin
  formulation, injection site, depth and volume of
  injection, skin temperature (warming), local
  massage and exercise.

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Types of insulin

• Rapid-acting insulin it begins to work about 5
  minutes after injection, peaks in around 1 hour,
  and continue to work for 2-4 hours (Lispro,
  Aspart).
• Regular or Short-acting insulin reach the
  bloodstream within 30 minutes after injection. It
  will peak anywhere from 2-3 hours after injection
  and will stay effective for around 3-6 hours.
• Intermediate-acting insulin (NPH) - reach the
  bloodstream within 2-4 hours after injection. It
  will stay effective for around 12-18 hours.
• Long-acting insulin (Glargin) this type of
  insulin will reach the bloodstream within 6-10
  hours after injection and will stay effective for
  20-27 hours.
• Premixed insulin

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Insulin

• Side-effects
• Hypoglycaemia
• Weight gain
• Peripheral oedema (insulin treatment causes salt
  and water retention in the short term)
• Insulin antibodies (animal insulins)
• Local allergy (rare)
• Lipodystrophy at injection sites

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Insulin dosing regimens

• Most people require two or more injections of
  insulin daily.
• Once-daily injections rarely achieve satisfactory
  glycaemic control are reserved either for some
  elderly patients or for those who retain
  substantial endogenous insulin secretion have a
  low insulin requirement.
• Twice- daily mixtures of short- and intermediate
  acting insulin is a commonly used regimen.
• Basal-Bolus A regimen of multiple injection of
  short- acting insulin before the main meals, with
  an appropriate dose of single daily intermediate-
  or long acting insulin.
• The dose of the insulin preparations is adjusted
  according to frequent monitoring of blood glucose
  levels. Blood glucose monitory should be
  intensified during intercurrent illness other
  stressful conditions (Sick Day rule)

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• Combined oral anti-diabetic therapy and insulin
• In patients with type 2 diabetes who are
  requiring increasing doses of oral anti-diabetic
  drugs, the introduction of a single dose of an
  intermediate- (e.g. isophane) or long-acting
  insulin analogue, administered at bedtime, may
  improve glycaemic control and delay the
  development of overt pancreatic ß-cell failure.
• Insulin Pump
• Transplantation
• Surgery

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• Thank You
• Question?