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

2

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)

4

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

5

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

6

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)

7

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

8

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

9

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

10

Type II DMType II DM

• 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

11

Type II DMType II DM

• Risk factors for developing type II DM:

Genetic profile

Age

Race

Obesity

Physical inactivity

Classification

12

Type II DMType II DM

• Usually associated with a variety of disorders:

Obesity

Atherosclerosis

Hyperlipidemia

Classification

Metabolic syndrome or syndrome X

13

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

14

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

15

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

16

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

17

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

18

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

19

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

20

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

21

Long Term ComplicationsLong Term Complications

22

Monitoring Parameter & Test to Guide Management

Monitoring Parameter & Test to Guide Management

• Urine ketone testing

• Plasma glucose

• Self monitoring blood glucose

• Glycosylated hemoglobin

23

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

24

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

25

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

26

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

27

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

28

Glycosylated HemoglobinGlycosylated Hemoglobin

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

29

Glycosylated HemoglobinGlycosylated Hemoglobin

• 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

30

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

31

Principles of ManagementPart I: General Principles

32

General PrinciplesGeneral Principles

• Goals of therapy

• Components of therapy

• Non-pharmacological therapy

• Patient education

• Prevent & treatment of complications

• Role of pharmacists in diabetes management

33

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

34

Components of TherapyComponents of TherapyGeneral Principles

35

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

36

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

37

Prevent & Treatment of Complications

Prevent & Treatment of Complications

• Foot care

• Annual eye exam

• Nephropathy

• Cardiovascular risk factors

General Principles

38

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

39

Principles of ManagementPart II: A.Insulin & its Clinical

Applications

40

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

41

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

42

ImmunogenicityImmunogenicity

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

• Species source is now the primary immunogenic component

• Beef > Pork > human

Insulin

43

UsesUses

• Type 1 diabetes

• Type2 diabetes (if nothing works)

• Pregnant diabetic patient

• Hyperkalemia

Insulin

44

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

45

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

46

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

47

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

48

Review of Newer AgentsReview of Newer Agents

• 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

49

Review of Newer AgentsReview of Newer Agents

• 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

50

Review of Newer AgentsReview of Newer Agents

• 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

51

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

52

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

53

Complications of Insulin TherapyComplications of Insulin Therapy

1. Hypoglycemia

• Causes:

Increase insulin dosage

Decrease caloric intake

Increased muscle utilization

Excessive alcohol

Insulin

54

Complications of Insulin TherapyComplications of Insulin Therapy

• 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

55

Complications of Insulin TherapyComplications of Insulin Therapy

2. Lipohypertrophy

3. Lipoatrophy

4. Allergic reactions

5. Weight gain

Insulin

56

Thank youThank you

57