Diabties

Pharmacotherapy of Diabetes

Mellitus

Ravinder Yadav

MD Pharmacology

Introduction

• Diabetes is a group of metabolic disorders

characterized by chronic hyperglycemia

associated with disturbances of carbohydrate,

fat and protein metabolism due to absolute or

relative deficiency in insulin secretion and/or

action

• Diabetes causes long term damage,

dysfunction & failure of various organs

Diabetes Mellitus • "Diabetes" comes from the Greek word for

"siphon", and implies that a lot of urine is

made.

• The second term,"mellitus" comes from the

Latin word, "mel" which means "honey", and

was used because the urine was sweet.

Diabetes In India

• According to the Indian Council of Medical

Research-Indian Diabetes study (ICMR-

INDIAB), a national diabetes study, India

currently has 63 million people with diabetes.

• India represents the world’s second largest

diabetes population after China.

• This is set to increase to over 100 million by

2030.

• The majority of people with diabetes (>90%)

have Type 2 diabetes (T2DM).

Classification of DiabetesProposed by ADA - 1997.

• Type I:

– Absolute Insulin Deficiency due to islet cell destruction

• Either immune mediated or idiopathic

• Type II:

– Relative insulin deficiency due to impaired -cell function

– Marked ↑ peripheral insulin resistance

• Type III: Other Specific types

• Type IV: Gestational Diabetes

Type 1 DM

• Type 1 diabetes is characterized by destruction of the

pancreatic beta cells, most likely due to combined

genetic, immunologic and possibly environmental

(e.g. viral) factors which contribute to cell

destruction.

• This is abnormal response of the body in which the

antibodies are direct against the normal tissues and

eventually there is damage to Islet of Langerhans ,

specific area of the pancreas that produce insulin,

reducing the production of insulin or totally no

production of insulin.

Type 2 DM

• Type 2 Diabetes Mellitus is a adult onset, and

non-insulin dependent. There are 2 main

problems related to insulin in type 2 diabetes,

first one is “insulin resistance “ (insulin do not

bind with the special receptor on cell surface)

and impaired insulin secretion (insulin

secreting glands release irregular amount of

insulin).

Differences between type-1 and type-2 Diabetes Mellitus

• Type 1• Young age• Normal BMI, not obese• No immediate family history• Short duration of symptoms

(weeks)• Can present with diabetic

coma (diabetic ketoacidosis)• Insulin required

• Type 2• Middle aged, elderly• Usually overweight/obese• Family history usual• Symptoms may be present

for months/years• Do not present with

diabetic coma• Insulin not necessarily

required

e

Other specific typesA) Genetic defects of Beta cell function

B) Genetic defects in Insulin action

C) Diseases of the Exocrine Pancreas

D) Secondary to Endocrinopathies

E) Drugs / Chemical induced

F) Infections

G) Uncommon form of Immune Mediated Diabetes.

H) Other Genetic Syndromes associated with Diabetes

MODY Syndromes

Lipo atrophic Diabetes

FCPDPancreatitis

TraumaNeoplasia

Cystic FibrosisHemochromatosis

AcromegalyCushings SyndromePheochromocytoma

Hyperthyroidism

SteroidsThiazidesDiazoxide

Beta BlockersThyroid Hormones

Congenital RubellaCMV

Anti insulin Receptor Antibodies

Down’s SyndromeTurners

Klinefelters

Gestational Diabetes•Gestational diabetes is caused when the insulin

receptors do not function properly and glucose

intolerance increases

•This is likely due to pregnancy related factors

such as the presence of human placental lactogen

that interferes with susceptible insulin receptors.

•Increased health risk to mother and baby

•Big baby,jaundice,still birth can occur for

untreated cases

•Goes away after birth, but increased risk of

developing Type 2 DM for mother and child

RISK FACTORS &SYMPTOMS

RISK FACTORS

Symptoms of Diabetes

• Polyuria - weakness

• Polydipsia - fatigue

• Polyphagia - blood sugar / glucose level

• weight loss - (+) glucose in urine (glycosuria)

nausea / vomiting

• changes in LOC

• Recurrent infection, prolonged wound healing

• Altered immune and inflammatory response, prone to

• infection (glucose inhibits the phagocytic action of WBC

• resistance)

- Genital pruritus – (hyperglycemia and glycosuria favor fungalgrowth : candidal infection – resulting in pruritus, common

• presenting symptom in women)

INVESTIGATION

– Fasting blood sugar

– Post prandial blood sugar

– HbA1C

– Lipid Profile – To diagnose dyslipidaemia

• RBS can be done only if the patient follows up

for the diagnostic tests after a meal

• Person to be tested should be on a normal diet for at least 3 days prior

to testing.

•The test should be done after an overnight fast of 8 – 10 hours (no

beverages including tea or coffee should be consumed),

•Draw a sample of blood after confirming fasting state of the patient.

Fasting Serum Glucose (mg/dl)

Diagnosis

Below 110 Normal

Between 110 and 126 Pre-diabetes

Above 126 Diabetes (Must be confirmed with a second fasting test)

Fasting Blood Sugar

Post Prandial Blood Sugar

• Following the collection of the fasting blood

sample for analysis of fasting serum glucose

(FSG). Patient is advised to have a normal

meal and return to the clinic after 2 hours

following the meal.

Post prandial blood sugar Diagnosis

< 140mg/dl Normal

140-200mg/dl Pre -diabetic

>200mg/dl Diabetic

HbA1C

• Person to be tested should be on a normal diet for at least 3 days prior to testing.

• The test should be done after an overnight fast of 8 – 10 hours

HbA1C Levels Diagnosis

4 – 6 Normal for those without diabetes

6.1-7 Target range for diabetics

>7 Poor control

Lipid profileResults of lipid profile Classification

LDL

< 100 optimal

100-129 Near optimal

130-159 Borderline high

160-190 High

>190 Very high

Serum triglycerides

< 150 Optimal

150-199 Borderline high

200-499 High

>500 Very high

HDL cholesterol

< 40 Low

> 60 High

TREATMENT GUIDELINES

Major Risk Factors (Exclusive of LDL Cholesterol)

• Cigarette smoking

• Hypertension (BP >140/90 mmHg or on antihypertensive medication)

• Low HDL cholesterol (<40 mg/dL)

• Family history of premature CHD

• Age (men >45 years; women >55 years)

LDL VALUES Risk factor Treatment goal

>130 CHD Pharmacologicaltheraphy

>160 +2 risk factors Pharmacological theraphy

>160-190 + 1 risk factor Life style modification

>190 +1 risk factor Pharmocologicaltheraphy

TREATMENT GUIDELINES

Insulin

Discovery of insulin

Patient leonard thomson.,, February 15, 1923

December 15 1922

The Miracle of Insulin

Structure of insulin

21 amino acids

30 AA

Difference between human, pork, beef insulin

Species A-chain B-chain

8th AA 10th AA 30th AA

Human THR ILEU- THR

Pork THR ILEU ALA

Beef ALA VAL ALA

Bioassay of insulin

• 1 IU reduces the BSL to 45 mg/dl in fasting rabbits

• 1 mg insulin = 28 IU

• Can also be measured by radioimmunoassay or enzyme immunoassay

Actions of insulin

Rapid actions Intermediary actions Long term

Sec / min Few hours > 24 hrs

E.gMetabolic actions

•↑ multiplication•↑ differentiation of cells • Imp role in intrauterine & extrauterinegrowth

Through DNAe.g• ↑ GLUT synthesis• Synthesis of enzymes for AA metabolism

Actions of insulin

• Metabolic:

– carbohydrate, lipid , protein, electrolyte

• Vascular

• Anti-inflammatory

• Fibrinolytic

• Growth

• Steroidogenesis

Carbohydrate metabolism

• Over all action of insulin is to ↓ glucose level

in blood

– ↑ Transport of glucose inside the cell

– ↑ Peripheral utilization of glucose

– ↑ Glycogen synthesis

– ↓ Glycogenolysis

– ↓ Gluconeogenesis

Lipid metabolism

• ↓ Lipolysis

• ↑ Lipogenesis

• ↑ Glycerogenesis

• ↓ Ketogenesis

• ↑ Clearance of VLDL & chylomicrons from

blood through enzyme Vascular Endothelial

Lipoprotein Lipase

Protein metabolism

• Facilitates AA entry and their synthesis into proteins and inhibit breakdown in muscles and other cellsls

Electrolyte metabolism

• ↑ transport of K+, Ca++, inorganic phosphates

Other actions

• Vascular actions:

– Vasodilation by Activation of endothelial NO production

• Anti-inflammatory action

– Especially in vasculature

• Decreased fibrinolysis

• Growth

• Steroidogenesis

Mechanism of action of insulin

Insulin Mediated Glucose Transport

G

INS

aa

InsulinReceptorComplex

INSaa

a subunit

subunit

Insulin molecule

Storage vesiclecontaining

GLUT 4

Glucose

Tyrosine Kinase Activation

Metabolised Stored as Glycogen

Fate of insulin

• Distributed only extracellularly

• Must be given parenterally

• Addition of zinc or protein decreases its absorption & prolongs the DOA

• Insulin released from pancreas is in monomeric form

• Half life of insulin = 5 -9 minutes

Different types of insulin preparations

• Conventional preparations of insulin

– Produced from beef or pork pancreas

– 1 % of other proteins

– Potentially antigenic

• Highly purified insulin preparations

– Gel filtration reduces or ion exchange

• Human insulins

• Newer insulin analogs

Conventional insulin preparations

Type Onset (Hr)

Peak (Hr)

DOA (Hr)

Short acting Regular insulin Semilente

0.5 -1 1

2-4 3-6

6-8 12-16

Intermediate acting

LenteIsophane(NPH)

1-2 8-10 20-24

Long acting Ultra lenteProtamine ZincInsulin (PZI)

4-6 14-18 24-36

Highly purified insulin preparations

• Single peak insulins

– Purified by gel filtration contain 50 to 200 PPM proinsulin

– Actrapid: purified pork regular insulin

– Monotard: purified pork lente

– Mixtard: purified pork regular(30%) + isophane(70%)

• Mono component insulins

– After gel filtration purified by ion exchange chromatography contain 20 PPM proinsulin

– Actrapid MC, Monotard MC

Human insulins

• Human (Actrapid, monotard, insulatard, mixtard)

• Obtained by recombinant DNA technology

• Advantages

– More water soluble as well as hydrophobic

– More rapid SC absorption , earlier & more defined

peak

– Less allergy

• Disadvantages

– Costly

– Slightly shorter DOA

Indications of human insulins

• Insulin resistance

• Allergy to conventional preparations

• Injection site lipodystrophy

• During pregnancy

• Short term use of insulin

Newer Insulin analogs

Type Onset Peak (Hr)

DOA (Hr)

Rapid

acting

Lispro

Aspart

Glulisine

5-15 min

10-15 min

5-15 min

1

1

1

3-5

3-5

5-6

Long acting Glargine

Detemir

Degludec

1-2 hrs

2-3 hrs

1-2 hrs

No peak

6-8 hr

No peak

24 hr

24 hr

42 hr

Insulin Lispro

• Produced by Inversing proline at B28 with lysine at B29.

• Forms weak hexamers , dissociate rapidly

• Needs to be injected immediately before or after meals

• Better control of meal time glycemia & lower incidence of PP hypoglycemia

• Insulin aspart:– Proline at B28 replaced by aspartic acid

– Change reduces tendency for self aggregation

• Insulin glulisine– lysine replaces aspargine at B3 & glutamic acid

replaces lysine at position B29

Insulin glargine

• Prepared by adding 1 glycine at A21 together with 2

arginine residues at end of B chain

• Improved Stability

• Much better bioavailabilty

• Smooth peakless effect is obtained

• Fasting & interdigestive BGL effectively lowered

irrespective of time of day

• Lower hypoglycemic episodes

• Cannot be mixed with other insulins

• Suitable for once daily injection

Insulin detemir• Soluble long acting basal insulin analog with

• Flat action profile and prolonged duration

• Threonine in B30 ommited & C14 fatty acid

chain attached to amino acid B29

• Prolonged action

– Strong self association

– Albumin binding

– Fatty acid side chain

Insulin analogs score over conventional insulins

• Less nocturnal hypoglycemia

• Less weight gain

• Better efficacy

• More physiological action profiles

• Less premeal lag time (0-15 mts)

• Lispro & Glulisine even after meals

• Better PP glucose control

• Improved predictability, tolerability, and flexibility

Adverse effects of insulin

• Hypoglycemia

• Local reactions

– Lipodystrophy

– Lipoatrophy

• Allergy

• Obesity

• Insulin induced edema

Uses of insulin

• Diabetes mellitus

– Must for type I diabetics

– Can be used in type II diabetics

• Diabetic ketoacidosis

• Hyperosmolar non ketotic hyperglycemic

coma

Indications of insulin in type II DM

• Primary or secondary failure of oral hypoglycemics

• Pregnancy

• Perioperative period

• CKD

• Steroid therapy

• LADA

• Fasting > 300 mgms HbA1c > 10

• Unintentional wt loss with or with out ketosis

• Type 2 with DKA ( severe beta cell dysfunction )

Recommended sites for S/C Insulin injections

Insulin resistance

• State in which normal amount of insulin produces subnormal amount of insulin response

– ↓ insulin receptors

– ↓ affinity for receptors

• May be acute or chronic

• Requirement of > 200 Units of insulin per day in absence of stress

• Common in type II diabetics & obese

Newer insulin delivery devices

• Prefilled insulin syringes

• Pen devices

• Jet injectors

• Inhaled insulin

• Insulin pumps

• External artificial pancreas

• Insulin complexed with liposomes: intraperitoneal, rectal, oral

40 units/ml100 units/ml

PEN INJECTORS

• Easy to carry

• Easier to accurately measure dose

• more expensive than vials

JET INJECTORSNeedleless system. Uses high pressure air to force a tiny

stream of insulin through the skin

Insulin Pump

Pro

• Simplified insulin

dosing

• Precise delivery

• Greater impact in those

with highest starting

A1c

• Slightly less insulin use

per day

Con

Inhaled Insulin (Exubera) Advantages

Improved pt convenience

Faster onset of action compared to Regular SC insulin

No needles risk of infection

Potential earlier onset of insulin therapy in Type 2 DM

Oral antidiabetic drugs

• Sulfonylureas

• Meglitinides

• Biguanides

• Thiazolidinediones

• a-glucosidase inhibitors

Sulfonylureas

I Generation

– Tolbutamide

– Chlorpropamide

II Generation

– Glipizide

– Gliclazide

– Glibenclamide (Glyburide)

– Glimepiride

Mechanism of action

• Release of insulin by acting on SUR1 receptors

• Primarily augment phase 2 of insulin secretion

• Presence of at least 30% functional -cells essential for their action.

• Minor action: ↓ glucagon secretion

• Extra pancreatic action: ↑sensitivity of peripheral tissue to insulin by ↑insulin receptors

Pharmacokinetics

• Well absorbed orally

• Highly bound to plasma proteins > 90%

• Have low volume of distribution

• Cross placenta C/I in pregnancy

• Metabolized in liver

• Excreted in urine

Daily dose & Duration of action

Sulfonylureas Doses No of doses/day

DOA(hrs )

1 Tolbutamide 0.5 – 2 g 2-3 6-8

2 Chlorpropramide 0.1 to 0.5 g 1 36 -48

3 Glibenclamide 5 to 15 mg 1-2 18-24

4 Gliclazide 40- 240 mg 1-2 12-24

5 Glipizide 5 to 40 mg 1-2 12-18

6 Glimepiride 1 to 6 mg 1 Upto 24

Individual Sulfonylurea

Sulfonylureas Special points

1 Tolbutamide Short acting, low potency , hypoglycemia least likely

2 Chlorpropramide ↑Hypoglycemia, ↑ADH , Disulfiram Like Reaction

3 Glibenclamide Potent but slow acting, may work when others fail

4 Gliclazide Antiplatelet, antioxidant action, may delay Retinopathy, less weight gain

5 Glipizide Fast acting, hypoglycemia & weight gain less likely, prefered in elderly

6 Glimepiride More extrapancreaatic action, less hyperinsulinemia, less hypoglycemia

GLIMEPIRIDE

1) Lesser risk of hypoglycemia

2) Relatively safe in elderly and mild renal failure

3) Antiplatelet and antifibrinolytic activity

4) Little or no weight gain

5) FDA approved combination therapy with insulin

6) Safe and effective for use in the pediatric population

7) ↑ Levels of plasma adiponectin & ↓ TNF α

8) Stimulates GLUT4 expression

Why Glibenclamide is more potent and

longer acting than other SU

1. May accumulate within cells and directly stimulate

exocytosis of insulin granules

2. Greater/longer binding to SUR-1 receptors

3. Slower absorption and distribution

4. Inhibition of hepatic insulinase

5. Suppression of several counter-regulatory hormones

6. More suppression of Hepatic Glucose Output

7. May stimulate insulin synthesis

Adverse effects

• Hypoglycemia:

• GI disturbances: Nausea, vomiting, metallic

taste, diarrhoea & flatulence

• Weight gain

• Hypersensitivity

• Not safe in pregnancy

• Chlorpropamide:

– cholestatic jaundice, dilutional hyponatremia,

antabuse reaction

Contraindications

1. Allergy to SU

2. Renal failure

3. Significant hepatic dysfunction

4. Severe infections, stress, trauma, major surgery,

CVA

5. Pregnancy (except Glibenclamide)

Selection of SU

Clinical conditions Agents

Fasting & postprandial

hyperglycemia

Long acting/Intermediate acting Su.

Only postprandial hyperglycemia Glipizide

Renal impairment Glipizide

GDM Glibenclamide

Elderly (> 65) Avoid Glibenclamide, chlorpropamide

Alcoholics Avoid chlorpropamide

DM & IHD Avoid Glibenclamide.

DM, HT & Edema legs Avoid chlorpropamide

Meglitinide analogs

• Quick & short acting insulin releasers

• MOA: same as Sulfonylureas but act through

different receptor SUR2

• Mainly used to control Post prandial

hyperglycemia

• Less hypoglycemia

Repaglinide

• Well tolerated in elderly patients and in renal

impairment

• Adverse effects:

– Mild headache, dyspepsia, arthralgia, headache

• Indicated in type II DM

• Dose : start 0.5mg with meals can ↑ 16mg/day

Nateglinide

• Stimulates first phase of insulin secretion

• More rapid acting & shorter duration than

repaglinide

• Mainly used in post prandial hyperglycemia

without producing late phase hypoglycemia

• Little effect on fasting BSL

• Adverse effects: dizziness, nausea, flu like

symptoms

• Dose: 60 to 180 mg TDS with meals

Biguanides

• Metformin & phenformin

• Little or no hypoglycemia

• Also improves the lipid profile in type II

diabetic patients

• Metformin dose = 0.5 to 2.5 g/day in 2-3

divided doses

Mechanism of action

• Suppress hepatic & renal gluconeogenesis

• ↑ uptake & utilization of glucose by skeletal

muscles which reduces insulin resistance

• Inhibit alimentary absorption of glucose

• Interfere with mitochondrial respiratory chain

& promote peripheral glucose utilization by

enhancing anaerobic glycolysis

METFORMIN - INDICATIONS

• Obese Type 2 Diabetes.

• Secondary Sulfonylurea Failure state.

• To reduce Insulin requirements.

• Can be combined with Sulfonylureas,

Glitazones, Insulin.

Adverse effects

• Anorexia, nausea, vomiting, diarrhoea

• Metallic taste

• Loss of weight

• Skin rashes

• Lactic acidosis: rare

• Vitamin B12 deficiency: due to malabsorption

Usually does not cause hypoglycemia even in

large doses

Contraindications of metformin

• Renal failure –( Sr. Crt > 1.5 / Crt. Clearance < 40 )

• Advanced Liver Disease.

• Alcohol abusers.

• Cardiac Disease.

• Pregnancy.

Thiazolidinediones (Glitazones)

Rosiglitazone & pioglitazone Selective agonists of PPAR

Bind to nuclear PPAR

Activate insulin responsive genes - regulate

carbohydrate & lipid metabolism

Sensitize the peripheral tissues to insulin

↓blood glucose by

↑ Glucose transport into

muscle & adipose tissue

Inhibit hepatic

gluconeogenesis

Promote

lipogenesis

Thiazolidinediones

• Hyperglycemia, hyperinsulinemia, and

elevated HbA1c levels are improved.

• Pioglitazone has no effect on LDL levels, ↓

triglyceride & ↑ HDL

• Rosiglitazone has inconsistent effect on lipid

profile it ↑ HDL & LDL levels

• The TZDs lead to a favorable redistribution of

fat from visceral to subcutaneous tissues.

• Pioglitazone:

– 15 to 45 mg once daily orally

• Rosiglitazone:

– 4 to 8 mg once daily orally

• Pt who benefit most are type II DM with

substantial amount of insulin resistance

• Also used in PCOD

• Monotherapy – Hypoglycemia rare

• Add-on Therapy – readjust dosage.

• Takes one month to act

Adverse effects

• Weight gain: due to fluid retention & edema

• ↑ Extracellular fluid volume

• Worsening of CHF

• ↑ Deposition of subcutaneous fat

• Mild anemia: due to hemodilution

• Hepatotoxicity : rare

• Rosiglitazone: ↑risk of fractures especially in

elderly women

Contraindications

• Liver disease

• Congestive heart failure

• Pregnancy

• Lactating mother

• Children

Alpha glucosidase inhibitors

• Acarbose

• Miglitol

• Voglibose

Acarbose

• Complex oligosaccharide

• Inhibits a-glucosidase as well as a-amylase

• Reduces postprandial hyperglycemia without

increasing insulin levels

• Regular use reduces weight

• In prediabetics reduces occurrence of type II

DM, hypertension & cardiac disease

• Dose: 50 to 100 mg TDS

• Given just before food or along with food

Adverse effects

• Flatulence, diarrhoea, abdominal pain

• Do not cause hypoglycemia by themselves but

may cause if used with Sulfonylureas

• If hypoglycemia occurs should not be treated

with routine sugar (sucrose),

• Glucose should be used

Contraindicated in inflammatory bowel disease

& intestinal obstruction

88

Voglibose

• Advantages over Acarbose and Miglitol

– 20-30 times more potent then acarbose

–Does not affect digoxin bioavailability unlike

acarbose

–No dosage adjustment required in renal

impairment patients unlike miglitol

– Superior tolerability

–Dose: 0.2 to 5 mg

Newer drugs for Type II DM

• GLP-1 Analogues

– Exenatide

– Liraglutide

• DPP-IV Inhibitors

– Sitagliptin

–Vildagliptin

–Alogliptin

• Amylin analog:

Pramlintide

Exenatide

• Synthetic GLP I analogue resistant to DDP IV

• ↑ Post prandial insulin release

• Supresses glucagon release

• Supresses appetite and slows gastric emptying

• injected SC twice daily 1 hour before meals

acts for 6 to 10 hours

• Nausea is important side effect

Sitagliptin

• Orally active inhibitor of DPP-4

• Prevents degradation of endogenous GLP-I

• Dose: 100mg a day

• Mainly used in post prandial hyperglycemia

• No action on weight and lipids

• Costly

Pramlintide

• Synthetic amylin analog

• Improves overall glycaemic control,↓ PPG

• Reduces BW : anorectic action

• Well tolerated

• Given SC before meals

• SE: GI disturbances/Less hypoglycemia when used alone

• Can be used in type I DM

COMPLICATIONS

Chronic ComplicationsSystems Effected Disease Health Concern

Eyes • Retinopathy • Glaucoma

• Cataracts

• Blindness

Blood Vessels • Coronary artery disease • Cerebral vascular disease • Peripheral vascular disease

• Hypertension

• Heart attack • Stroke • Poor circulation in feet

and legs

• Heart attack, stroke,

kidney damage

Kidneys • Renal insufficiency

• Kidney failure

• Insufficient blood filtering

• Loss of ability to filter blood

Nerves • Neuropathies

• Autonomic neuropathy

• Chronic pain • Poor nerve signaling to

organ systems

Skin, Muscle, Bone • Advanced infections • Cellulitis

• Gangrene

• Amputation

Acute Complications

• Diabetic keto-acidosis (DKA)

• Insulin shock

• Hyperglycemic, hyperosmolar,

non-ketotic (HHONK) coma

• Dawn phenomenon

• Somogyi effect

D.K.A.

PATHOPHYSIOLOGY

NO INSULIN

MARKED HYPERGLYCEMIA

GLUCOSURIA

WEIGHT

LOSS

OSMOTIC

DIURESIS

POLYURIA

CELLULAR

HUNGER

POLYPHAGIA

POLYDIPSIA

LIPOLYSIS

OSMOTIC

DEHYDRATION

D.K.A.

Sign and Symptoms;

• S/sx of dm +

• Ketonuria

• Metabolic acidosis

• Kussmaul’s respiration

• Acetone breath

• Flushed face

• Tachycardia

• Circulatory collapse , coma and death

INSULIN SHOCK

Low blood sugar

Cause:

• Overdose of exogenous insulin

• Eating less

• Overexertion without additional calorie intake

INSULIN SHOCK

• S/SX:

• PARASYMPATHETIC– HUNGER

– NAUSEA

– HYPOTENSION

– BRADYCARDIA

• CEREBRAL– LETHARGY,

– YAWNING

– SENSORIUM CHANGES

• SYMPATHETIC

– IRRITABILITY

– SWEATING

– TREMBLING

– TACHYCARDIA

– PALLOR

• CLINICAL FINDING :

• BLOOD GLUCOSE BELOW 55-60 mg%

Hyperglycemic Hyperosmolar Non-

Ketotic Coma (HHNC)• can occur when the action of insulin is severely

inhibited

• seen in pts. w/t T2DMPrecipitating factors:

infection, renal failure, MI, CVA, GI hemorrhage,

pancreatitis, CHF, TPN, surgery, dialysis, steroids

S/Sx:

polyuria oliguria (renal insufficiency)

lethargy

temp, PR, BP, signs of severe fluid deficit

Confusion, seizure, coma

Blood glucose level > 600 mg/100 ml.

Interventions for DKA and

Hyperosmolar Coma

• Regular insulin IV push or IV drip

• 0.9% NaCl IV – 1 L during the 1st hr, 2-8 L over 24

hrs.

• administer sodium bicarbonate IV to correct acidosis

• Monitor electrolyte levels, esp. serum K+ levels

• administer K+, monitor UO hourly (30ml/hr)

SOMOGYI EFFECT

TOO MUCH INSULIN

HYPOGLYCEMIA

GLUCAGON IS RELEASED

LIPOLYSIS

GLUCONEOGENESIS

GLYCOGENOLYSIS

REBOUND

HYPERGLYCEMIA

+

KETOSIS

DAWN PHENOMENON

• The "dawn effect," also called the "dawn

phenomenon," is the term used to describe an

abnormal early-morning increase in blood

sugar (glucose) — usually between 2 a.m. and

8 a.m. in people with diabetes.

CHRONIC COMPLICATIONS OF

DIABETES MILLETUS• Degenerative changes in the vascular system

– Atherosclerosis

• Neuropathy from

– Vascular insufficiency

– Hyperglycemia

• Eye complications from anoxia

– Cataract

– Diabetic retinopathy

– Retinal detachment

Interventions and foot care practices

–Cleanse and inspect the feet daily.

–Wear properly fitting shoes.

–Avoid walking barefoot.

–Trim toenails properly.

–Report nonhealing breaks in the skin.

Wound Care

• Wound environment

• Debridement

• Elimination of pressure on infected area

• Growth factors applied to wounds

SUMMARY

• Treatable, but not curable.

• Preventable in obesity, adult client.

• Controllable- DIET and EXERCISE

• Diagnostic Tests

• Signs and symptoms of hypoglycemia and hyperglycemia.

• Treatment of hypoglycemia and hyperglycemia – diet and oral hypoglycemics.

Monitoring, teaching and assessing for complications.

“Of course too much is bad for

you”

THANK

YOU