Diabetes MellitusFifth Stage-Medicine

Dr. Sarbast Fakhradin

MBChB, MSc Diabetes Care & Management

Comprehensive diabetes care of type 2 DM

• 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

• Patient education & follow up: DAFNE & DESMOND

Blood glucose monitoring;Target Preprandial capillary plasma glucose (70-130 mg/dl)

Target postprandial capillary plasma glucose (< 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

• 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 < 130/80

– Smoking & alcohol

– Hypoglycemic episodes.

– Psychological support

– Target Lipid profile: Cholesterol< 200mg/dl,

– LDL < 100 mg/dl,

TG < 150 mg/dl

HDL> 40 mg/dl.

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.

• The glycaemic index (GI) of a carbohydrate-containing 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.

• Recommended composition of diet for people with diabetes:

• CHO 40-65%

• Fat < 35% ( saturated <10%)

• Protein 10-15%

• Fruit/Vegetable 5 portions daily

Anti-Diabetic Medications • Oral Agents:1. Biguanides (Metformin)

2. Insulin Secretagogues – Sulphonylureas (Gliclazide)

3.Insulin Secretagogues – Non-sulphonylureas (Repaglinide)

4. DPP4 inhibitor (Sitagliptin)

5. α-glucosidase inhibitors (Acarbose)

6. Thiazolidinediones (TZDs) (Pioglitazone)

• Injections:• 1. Insulin

• 2. GLP-1 agonist (Incretin mimetic) Exenatide & Liraglutide

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.

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.

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.

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).

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.

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.

Thiazolidinediones (pioglitazone) • Bind and activate peroxisome proliferator-activated receptor-γ

(PPARγ 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?

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.

Oral hypoglycaemics

Glucose output

Insulin resistance

Biguanides

Insulin secretion

Sulfonylureas/meglitinides

Rate of carbohydrate breakdown/absorption

-glucosidase inhibitors

Insulin resistance

Thiazolidinediones

Mechanisms of glucose-stimulated insulin secretion

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.

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.

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.

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.

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.

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

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

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)

• 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 β-cell failure.

• Insulin Pump• Transplantation• Surgery

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