Diabetes Mellitus (DM) Part I PHCL 442 Hadeel Al-Kofide MSc 1

Diabetes Mellitus (DM)Part I

PHCL 442

Diabetes Mellitus (DM)Part I

PHCL 442

Hadeel Al-Kofide MSc

1

Topics we will cover in DMTopics we will cover in DM

• Definition & Epidemiology• Carbohydrate metabolism• Classification• Signs & symptoms• Diagnosis• Long term complications• Monitoring parameter & test to Guide management• Principles of management:

Part I: General principlesPart II: a. Insulin & its clinical applications

b. Oral anti-diabetic agents• Prevention & management of diabetes complications

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Definition & EpidemiologyDefinition & Epidemiology

• A syndrome caused by relative or absolute lack of insulin

• Glucose intolerance & alteration in lipid metabolism

• Diabetes is the 6th leading cause of death in U.S

• Leading causes of blindness in adults aged 20-74

• Leading causes of end – stage renal disease

• The CDC has declared an epidemic of diabetes

3CDC: Center of Disease Control & Prevention

Carbohydrate MetabolismCarbohydrate Metabolism

• Homeostatic mechanisms maintain plasma glucose between 55 & 140 mg/dl

• A minimum concentration of 40 – 60 mg/dl needed for CNS (uses glucose as its primary energy source) & it is independent of insulin for glucose utilization

• Muscle & fat also used glucose as an energy source, but these tissues require insulin for glucose uptake

• When glucose concentration exceeds the reabsorptive capacity of the kidney (180 mg/dl)

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Carbohydrate MetabolismCarbohydrate Metabolism

Postprandial Metabolism

Insulin release (anabolism)

Glucose

Turns on

Glycogen

AA Protein

FFA TG

Fasting Metabolism

Counterregularty hormones releaseGluccagon

EpinephrineCortisol

Growith hormone

GlycogenolysisGluconeogensis

↑ Glucose

Shuts off

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Carbohydrate Metabolism & DMCarbohydrate Metabolism & DM

• Blood glucose concentration remain elevated after a meal with the absolute or relative lack of insulin

• Since glucose is inaccessible to cells fasting metabolism is triggered

• Further increase in glucose with glycogenolysis & gluconeogenesis

• Diabetes video

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http://labtestsonline.org/understanding/conditions/insulin_resistance.html

ClassificationClassification

• Type I DM

• Type II DM

• Gestational DM

• Other specific types of diabetes due to other causes, e.g., genetic defects in cell function, genetic defects in insulin action, diseases of the exocrine pancreas (such as cystic fibrosis)

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Type I DMType I DM

• Known as ‘juvenile’, or Insulin-dependent DM (IDDM)

• Accounts for 5% - 10% of total diabetes cases

• Onset is between 8-14 yrs old usually presenting with ketosis

• Regarded as an auto-immune disease (Antibodies to islet cells &/or insulin)

• Gradual loss of beta cell function until no longer able to synthesize adequate insulin to control blood sugar

• Presenting symptoms are polydipsea, polyurea, polyphagia & weight loss

Classification

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Type I DMType I DM

• Patients are most often lean

• Patients must rely on exogenous sources of insulin

• Honey-moon phase:

After weeks of diagnosis patients have period of remission (decrease in blood glucose concentration)

Endogenous insulin secretion recovers temporarily

May last for weeks, months or a year

Continue on low dose insulin to prevent resistance & allergy

Classification

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Type II DMType II DM

• Formerly known as “adult-onset” or Non-insulin dependent diabetes mellitus (NIDDM)

• 90% of total cases

• Very strong genetic component

• 80% with Type 2 are obese

• Defect in insulin secretion:

Tissue resistance to insulin

Increase in hepatic glucose production

Classification

↑ Insulin↑ Glucose

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• Usually diagnosed through routine hospital visit

• Mild symptoms & gradual

• Weight loss is uncommon

• Treatment:

Exercise

Diet

Oral hypoglycemic agents

Last thing can add insulin

Classification

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• Risk factors for developing type II DM:

Genetic profile

Age

Race

Obesity

Physical inactivity

Classification

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• Usually associated with a variety of disorders:

Obesity

Atherosclerosis

Hyperlipidemia

Classification

Metabolic syndrome or syndrome X

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Gestational DM (GDM)Gestational DM (GDM)

• Affect around 7% of pregnancies

• Any carbohydrate intolerance with first recognition during pregnancy

• Risk on fetus:

Neonatal death

Macrosomia (infant weight > 9 pounds)

• Risk on mother:

Greater chance for cesarean section

HTN

Classification

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Signs & SymptomsSigns & Symptoms

• The 3 Ps

• Blurred vision

• Ketoacidosis

• Fatigue

• Weight loss

Type I DM:More common to see ketoacidosis &

weight loss

Type II DM:Usually mild symptoms & patient may

only complain of fatigue

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DiagnosisDiagnosis

• First look at S & S

• Fasting blood glucose

• Random blood glucose

• OGTT (oral glucose tolerance test)

• How to differ between type I & II DM?

• GDM diagnosis

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Type I & II DMType I & II DMCriteria for the diagnosis of diabetes

1FPG ≥126 mg/dl (7.0 mmol/l). Fasting is defined as no caloric intake for at least 8 h

OR

2

Symptoms of hyperglycemia & a casual plasma glucose 200 mg/dl (11.1 mmol/l). Casual is defined as any time of day without regard to time since last meal. The classic symptoms of hyperglycemia include polyuria, polydipsia, & unexplained weight loss

OR

3

2-h plasma glucose 200 mg/dl (11.1 mmol/l) during an OGTT. The test should be performed as described by the World Health Organization, using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water

Diagnosis

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Type I OR Type II DM?Type I OR Type II DM?

• Young (<30), lean & with S & S and high blood glucose usually type I

• Ketonuria strongly support the diagnosis of type I DM

• 8 – 45% of children diagnosed with DM have type II DM

• Obesity usually goes with type II DM

• In type II DM there is a strong family history

• C-peptide test: if (+) type II DM, if (-) type I DM Why?

Diagnosis

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GDMGDM

• Women at very high risk for GDM should be screened as soon as possible after the confirmation of pregnancy

• Criteria for very high risk are:

Severe obesity

History of GDM or delivery of large-for-gestational-age infant

Presence of glycosuria

Diagnosis of PCOS

Strong family history of type 2 diabetes

• If not found to have diabetes early in pregnancy, should undergo GDM testing at 24–28 weeks of gestation

Diagnosis

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GDMGDM

• Low risk status, which does not require GDM screening, is defined as women with all of the following characteristics:

Age 25 years

Weight normal before pregnancy

Member of an ethnic group with a low prevalence of DM

No known diabetes in first-degree relatives

No history of abnormal glucose tolerance

No history of poor obstetrical outcome

Diagnosis

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GDMGDM

• A diagnosis of GDM requires at least two of the following plasma glucose values:

Fasting: ≥95 mg/dl (≥ 5.3 mmol/l)

1 h: ≥ 180 mg/dl (≥ 10.0 mmol/l)

2 h: ≥ 155 mg/dl (≥ 8.6 mmol/l)

3 h: ≥ 140 mg/dl (≥ 7.8 mmol/l)

Diagnosis

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Long Term ComplicationsLong Term Complications

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Monitoring Parameter & Test to Guide Management

Monitoring Parameter & Test to Guide Management

• Urine ketone testing

• Plasma glucose

• Self monitoring blood glucose

• Glycosylated hemoglobin

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Urine Ketone TestingUrine Ketone Testing

• Type I DM & GDM

• May indicate ketoacidosis

• If blood glucose > 300 mg/dl or in acute illness must test for ketones

Monitoring

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Plasma GlucosePlasma Glucose

• Normal fasting blood glucose (FBG) 70 – 100 mg/dl

• FBG reflect hepatic glucose production (fasting state)

• Also can use random or postprandial blood glucose measurement

• To convert from mg/dl to mmol/L divide by 18

Monitoring

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Self Monitoring Blood GlucoseSelf Monitoring Blood Glucose

• SMBG is the day-to-day monitoring choice for all patients with DM

• Problem:

Expensive

Patient must understand how to use it

Monitoring

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Self Monitoring Blood GlucoseSelf Monitoring Blood Glucose

• Patients in whom SMBG is particularly valuable:

Type I DM: it helps patient to correlate between means, exercise & insulin dosing with blood glucose concentration

Pregnant: Infant morbidity & mortality is associated with mother’s glucose control

Patients having difficulty recognizing hypoglycemia

Patients on intensive insulin therapy: patients who are on multiple daily dosing of insulin or insulin pump

Monitoring

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Glycosylated HemoglobinGlycosylated Hemoglobin

• Non – enzymatic irreversible glycosylation of hemoglibine A circulating in blood, amount formed is related to degree of hyperglycemia

• Measures by % of hemoglobin

• It indicates glycemic control over 2-3 months

• Adjunct in assessing overall glycemic control

• In normal patients 4-6%

• A 1% change in the glycosylated hemoglobin can represent a 25-35 mg/dl change in the mean blood glucose

Monitoring

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Hgb A1C 5% 6% 7% 8% 9% 10% 11% 12%

Average Blood glucose in mg/dl

90 120 150 180 210 240 270 300

Monitoring

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• Advantages:

No need any special patient preparations (e.g. fasting)

Not subject to acute changes in insulin dosing, exercise or diet

• It does not replace the daily monitoring of blood glucose, because daily monitoring is required to adjust acute changes in glucose level and according to it plan meals & insulin dosing

Monitoring

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Glycemic Goals According to ADAGlycemic Goals According to ADA

A1C < 7%

Preprandial plasma glucose 70–130 mg/dl (3.9–7.2 mmol/l)

Peak postprandial plasma glucose

<180 mg/dl (<10.0 mmol/l)

Monitoring

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Principles of ManagementPart I: General Principles

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General PrinciplesGeneral Principles

• Goals of therapy

• Components of therapy

• Non-pharmacological therapy

• Patient education

• Prevent & treatment of complications

• Role of pharmacists in diabetes management

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Goals of TherapyGoals of Therapy

• Keep patient asymptomatic

• Prevent long term complications

• Maintain patient near euglycemia

• Achieve & maintain an appropriate body weight

• Maintain normal growth & development in children

• Enhance patient & self reliance in management of the disease

• Eliminate or minimize all cardiovascular risk factors

General Principles

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Components of TherapyComponents of TherapyGeneral Principles

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Non-Pharmacological TherapyNon-Pharmacological Therapy

• Diet:

Moderate caloric restriction

Moderate weight loss

Protein: 10 – 20% of daily caloric intake

< 10 % saturated fats and < 10 % polyunsaturated fats

< 300 mg cholesterol

20-35 gm fiber

• Exercise

General Principles

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Patient EducationPatient Education

• Educate the patient and family about disease & treatment

• Instruct how to use insulin

• Instruct patient on method of glycemic control

• Set realistic goals

• Formulate a plan for achieving glycemic control

• Obtain agreement with the patient regarding goals & treatment & provide supportive follow up

General Principles

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Prevent & Treatment of Complications

Prevent & Treatment of Complications

• Foot care

• Annual eye exam

• Nephropathy

• Cardiovascular risk factors

General Principles

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Role of PharmacistsRole of Pharmacists

• Pivotal role in the overall management of the diabetic patient

• Obtain patient history & pertinent information

Record & review all medication including OTCs & herbal

Monitor patient’s adherence to their therapy

Counsel on disease state, HBGM, injections, oral medications

• Assess outcomes

• Collaborate with other healthcare professionals

• Documentation is key

General Principles

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Principles of ManagementPart II: A.Insulin & its Clinical

Applications

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InsulinInsulin

• Immunogenicity

• Uses

• Insulin Types & Their Physical Properties

• Review of newer agents

• Factor Altering Insulin Action

• Stability

• Complications of Insulin Therapy

• Application on insulin in clinical practice

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InsulinInsulin

• A hormone secreted from the pancreatic β cell in response to glucose & other stimulants like amino acids

• Made up of 2 polypeptide chains which are connected by 2 disulfide bonds

Insulin

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ImmunogenicityImmunogenicity

• Now impurities are rare & most patients use human insulin (less hypersensitivity)

• Species source is now the primary immunogenic component

• Beef > Pork > human

Insulin

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UsesUses

• Type 1 diabetes

• Type2 diabetes (if nothing works)

• Pregnant diabetic patient

• Hyperkalemia

Insulin

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Types of InsulinTypes of Insulin

• Rapid acting (ultra-short acting) insulin

Insulin lispro, aspart & glulisine

• Short acting insulin

• Intermediate acting insulin

NPH, lente & NPL

• Long acting insulin:

Ultralent, glargine & detemir

• Premixed

Insulin

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Types of InsulinTypes of InsulinInsulin Onset Peak Duration Appearance

Short acting Lispro (Humalog)Aspart ( Novolog)Glulisine(Apidra)Regular

15 min5-15 min15-20 min30-60 min

30-90 min1-3 hrs0.5-2hrs2-4 hrs

3-4 hrs3-5 hrs

5-7 hrs

ClearClear

Clear

Intermediate acting

NPHLente

1-1.5 hrs1-3 hrs

4-12 hrs6-14 hrs

24 hrs24 hrs

CloudyCloudy

Long acting UltralenteGlargine (lantus)detemir (Levemir)

6 hrs1.5 hrs1-3 hrs

18-24 hrsFlat

36 hrs24 hrs24 hrs

CloudyClear

Insulin

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Types of InsulinTypes of InsulinInsulin

Available insulin pre-Mixtures Brand Names

NPH/Regular mixture (70/30 %)Humulin 70 / 30Novolin 70/30

NPH/ RegularMixture ( 50/50 %) Humulin 50/50

NPL/Lispro mixture ( 75 / 25 %) Humalog 75/25

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Review of Newer AgentsReview of Newer Agents

• Lispro , aspart or glulisine insulin: more closely simulates physiologic insulin secretion relative to meals

• Advantages :

Decreases post-prandial hypoglycemia

Fewer overall occurrence of hypoglycemia, less nocturnal hypoglycemia

Greater flexibility

Insulin

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• Disadvantages:

Risk of hypoglycemia if no meal within 15 minutes of dose

Will need to combine with a longer acting insulin for optimal BS Control

If mixed with another insulin give immediately after mixing

Hyperglycemia / ketosis may occur more rapidly if insulin delivery is interrupted

Insulin

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• Insulin glulisine:

• When used in a pump, do not mix insulin glulisine with other insulins or with a diluent

• If glulisine is mixed with NPH human insulin, draw the glulisine into the syringe first. Make injection immediately after mixing

• Do not mix glulisine with insulin preparations other than NPH

Insulin

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• Glargine & Detimir insulin:

• Advantages:

Provided 24 hour coverage with a constant absorption pattern & no pronounced peak

May be beneficial in patients suffering from nocturnal hypoglycemic episodes

• Disadvantages:

Can Not be mixed with any other insulin

Cost

Insulin

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Factor Altering Insulin ActionFactor Altering Insulin Action

• Route of administration

• Site of injection

• Temperature

• Exercises / massage

• Preparation / mixtures

• Dose

• Patient compliance

• Patient errors

• Irregular diet & excesses

• Renal function

• Stress

• Drugs

Insulin

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StabilityStability

• Stable at room temperature for one month

• Refrigerate vials not in use & do NOT freeze

• Opened insulin vials in refrigerator discarded after 90 days

• Insulin prefilled syringes is stable for 28 days refrigerated

• Mixture stability

Regular / NPH

Regular / Lente or Ultralente

Lispro / NPH or Lentre or Ultralente

Glarginel/all other insulins

Insulin

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Complications of Insulin TherapyComplications of Insulin Therapy

1. Hypoglycemia

• Causes:

Increase insulin dosage

Decrease caloric intake

Increased muscle utilization

Excessive alcohol

Insulin

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• Signs / symptoms

Termors, tachycardia, diaphorersis, confusion slurred speech, drowsiness, etc

Beta- Blockers can decrease responsiveness to hypoglycemia due to blocking sympathetic warning symptoms

• Treatment

15 –30 gm carbohydrate follow with complex carbohydrate

Glucagon for severe patients

Insulin

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2. Lipohypertrophy

3. Lipoatrophy

4. Allergic reactions

5. Weight gain

Insulin

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Thank youThank you

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Documents

Diabetes Mellitus (DM) Part I PHCL 442 Hadeel Al-Kofide MSc 1