DIABETES

MELLITUS

Vy Vu
Doctor of Pharmacy
Hutech University
07/29/2020
OBJECTIVES
❑ Examine pathophysiology of diabetes
❑ Classify prediabetes and diabetes types
❑ Understand the criteria for diagnosing diabetes
❑ Learn acute and chronic diabetes complications
❑ Explore the current pharmacologic recommendation for diabetes

7/15/2020 Vy Vu
RESOURCES
❑ Lee-Ellen C. Copstead & Jacquelyn L. Banasik. Pathophysiology. 5E,
2013. Chapter 41. Diabetes Mellitus. Pp 817-832

❑ Laurence Brunton. Goodman and Gilman’s The Pharmacological

Basis of Therapeutics. Chapter 47: Endocrine Pancreas and
Pharmacotherapy of Diabetes Mellitus and Hypoglycemia. Pp 863-886

❑ American Diabetes Association: Standards of Medical Care in

Diabetes 2020.3

7/15/2020 Vy Vu
EPIDEMIOLOGY
❑ 34.2 million Americans (10.5% of the population) had diabetes in 2018
▪ Type 1 : 5-10%
▪ Type 2: 90-95%
❑ 88 million people aged 18 years or older have diabetes (34.5% of the adult
US population)
❑ 7th leading cause of death in the US (83,564 death in which diabetes was
the underlying cause in 2017)
❑ 422 million people with diabetes worldwide in 2014
❑ Cost of diagnosis was $327 billion in 2017
CDC – National Diabetes Statistics Report 2020
WHO – Diabetes June 2020

7/15/2020 Vy Vu
 PANCREAS
Location
❑ Behind the stomach in the
upper left abdomen.
❑ Islet of Langerhans

Pancreas location
PANCREAS
Islet of Langerhans
❑ Beta Cells
o Insulin
o Amylin
❑ Alpha Cells
o Glucagon
❑ Delta Cells
o Somatostatin
Figure: Islet of Langerhans in the pancreas
INSULIN SECRETION

Figure : Process of glucose exocytosis

Lee-Ellen C. Copstead & Jacqueline Banasik. Pathophysiology. Diabetic Mellitus 2012

7/15/2020 Vy Vu
INSULIN SECRETION PATTERN

Figure : Physiology insulin secretion pattern in basal (fasting state)

7/15/2020 and post-prandial (fed state) Vy Vu
Dipiro. Pharmacotherapy: A Pathophysiologic Approach, 10E.
INSULIN ACTION
❑ Promoting the uptake, use
and storage of glucose, lipids,
and amino acids
❑ Stimulate glycogenesis,
lipogenesis, and protein
synthesis
❑ Suppresses hepatic glucose
production/ Stimulates glucose
uptake by peripheral tissues
Figure : Synthesis and processing insulin
Goodman and Gilman_s. The pharmacologic basis of
Vy Vu
7/15/2020 Therapeutic 13E, 2017.
AMYLIN ACTION
❑ Co-secreted with Insulin
❑ Slows gastric emptying promoting satiety
❑ Inhibit inappropriate secretion of
glucagon

7/15/2020 Vy Vu
GLUCAGON
❑Opposes the action of insulin and
stimulates hepatic glucose production
❑Response to hypoglycemia state

7/15/2020
GLUCOSE HOMEOSTASIS

Figure 4: Insulin, Glucagon, and glucose homeostasis

Goodman and Gilman_s. The pharmacological basis of therapeutics, 13E 2017
GLUCOSE HOMEOSTASIS

Feeding state
Glycogenesis
Fasting state Lipogenesis
Glycogenolysis
Gluconeogenesis
Lipolysis

7/15/2020 Vy Vu
PATHOPHYSIOLOGY
❑ The autoimmune destruction of β cells

❑ Insulin resistance
▪ Definition: normal amounts of insulin are inadequate in
producing a normal insulin response
▪ Insulin receptors begin to “down-regulate”
PATHOPHYSIOLOGY
Site of resistance
▪ Liver: basal and post prandial
▪ Muscle: 80% of total body glucose uptake –
primary state of insulin resistance
▪ Adipose tissue
Insulin is a potent inhibitor of lipolysis → chronically high
levels of FFA impaired insulin secretion.
DIABETES CLASSIFICATION
❑ TYPE 1 DIABETES
▪ Autoimmune β cell destruction
▪ Absolute insulin deficiency

❑ TYPE 2 DIABETES
• Processive loss of β cell insulin secretion
• Insulin resistance

Figure: Pathogenesis of type 2 diabetes

Porth. Essentials of Pathophysiology Concepts of
Altered Health States. 4E
7/15/2020 Vy Vu
COMPARE TYPE 1 AND TYPE 2 DIABETES
Type 1 Type 2

Age 75% will develop the disorder before age 20 Mostly in adults

Onset Abrupt Gradual

Symptoms Polyuria, polydipsia, polyphagia (3P) Usually asymptomatic for years

Weight loss
Etiology Autoimmune destruction of pancreatic B cells Insulin resistance, with inadequate
B cell function to compensate
Acute complications Ketoacidosis Hyperglycemia

Pharmacologic Insulin mostly Antidiabetic Agents and Insulin

intervention

7/15/2020 Vy Vu
TYPE OF DIABETES
❑ GESTATIONAL DIABETES
▪ 2nd or 3rd trimester of pregnancy
▪ Not clearly overt diabetes

❑ OTHER TYPES
▪ Monogenic diabetes syndromes
▪ Drug-or chemical-induced diabetes

7/15/2020 Vy Vu
DIABETIC RISK TEST

7/15/2020 Vy Vu
TESTING ASYMPTOMATIC ADULTS

BMI ≥ 25 kg/m2 or ≥ 23 kg/m2 in Asian Americans with ≥ 1 of

these risk factors
❑ 1st degree relative with ❑ Physical inactivity
diabetes ❑ High-risk race/ethnicity
❑ History of CVD ❑ Other conditions: severe
❑ Hypertension obesity, acanthosis nigricans
❑ HDL < 35 mg/dL or TG > 250
mg/dL
❑ Polycystic ovary syndrome
7/15/2020 Vy Vu
DIAGNOSIS

PRE-DIABETES

GESTATIONAL
DIABETES
DIABETES

7/15/2020 Vy Vu
 A1C – GLYCATED HEMOGLOBIN
❑ Average blood glucose for the past 2-3 months
❑ Does NOT replace daily monitoring of BG
❑ What conditions alter the relationships between A1C and glycemia?
▪ Sickle cell disease
▪ Pregnancy
▪ Glucose-6-phosphare dehydrogenase deficiency
▪ HIV
▪ Hemodialysis, recent blood loss or transfusion
▪ Erythropoietin therapy

ADA. Standards of Medical care in diabetes. Volume 43, supplement 1, Jan 2020
7/15/2020 Vy Vu
CORRELATION BETWEEN A1C AND PLASMA GLUCOSE
A1C (%) Mean Plasma Glucose (mg/dl)
6 126 (100 – 152)
7 154 (123 – 185)
8 183 (147 – 217)
9 197 (170 – 249)
10 240 (193 – 282)
11 269 (217 – 314)
12 298 (246 – 347)

Nathan DM, et al. Translating the A1C assay into estimated average glucose value. Diabetic Care. 2008; 31:1-6

7/15/2020 Vy Vu
PREDIABETES DIAGNOSING CRITERIA

FBG 100 – 125 mg/dL

OR
2h PG During 75g OGTT 140 – 199 mg/dL
OR
A1C 5.7 – 6.4%

7/15/2020 Vy Vu
 DIABETES DIAGNOSING CRITERIA
FBG ≥ 126 mg/dL In the absence of
OR unequivocal
hyperglycemia,
2h PG ≥ 200 mg/dL during OGTT diagnosis requires
OR 2 abnormal test
A1C ≥ 6.5% results from the
same sample or in
OR 2 separated test
In a patient with classic symptoms of hyperglycemia or samples
hyperglycemic crisis, a random plasma glucose ≥ 200 mg/dL

7/15/2020 Vy Vu
GESTATIONAL DIABETES DIAGNOSING

Figure: Screening for and

diagnosis of GDM

7/15/2020
FREQUENCY OF TESTING
❑ Pre-diabetes patients: annual
❑ GDM patients: lifelong testing at least every 3 years
❑ Other patients: testing should begin at 45-year-old

7/15/2020 Vy Vu
SYMPTOMS OF DIABETES
Hypoglycemia Hyperglycemia
❑Shaking ❑3 P’s:
❑Tachycardia Polyuria
❑Sweating Polydipsia
❑Headache Polyphagia
❑Impair vision ❑Blurred vision
❑Weakness/fatigue ❑Dry skin
❑Irritability ❑Nausea
❑Drowsiness

7/15/2020 Vy Vu
DRUGS THAT PROMOTE HYPER/HYPOGLYCEMIA
HYPERGLYCEMIA HYPOGLYCEMIA
Glucocorticoids, thyroid hormone B Adrenergic antagonists
Antipsychotics (atypical, others) Theophylline
Protease inhibitors Salicylate, NSAIDs
Epinephrine Ethanol
Thiazide diuretics Bromocriptine
Hydantoins (phenytoin, other) LiCl
Opioids (fentanyl, morphine) Pentamidine
Diazoxide, nicotinic acid
Interferons, amphotericin B
Acamprosate, basiliximab, asparaginase

7/15/2020 Vy Vu
ACUTE COMPLICATIONS - HHS/DKA
❑DKA = Diabetic ketoacidosis
▪ Type 1 diabetic patients or late stage of type 2

❑HHS = Hyperosmolar hyperglycemic sate

▪ Type 2 diabetic patient

7/15/2020 Vy Vu
DKA/HHS – PRECIPITATING CAUSES
❑New Diagnosis of Diabetes Mellitus
❑Inadequate Therapy
▪ Insulin
▪ Oral therapy
▪ Limited access of care
❑Infection
▪ Pneumonia and UTIs
❑Other factors?

7/15/2020 Vy Vu
DKA/HHS – DIAGNOSIS

DKA diagnosis criteria HHS diagnosis criteria

❑ Blood glucose >250 mg/dL ❑ Serum glucose > 600 mg/dL

❑ Arterial pH =< 7.3 ❑ Arterial pH > 7.3
❑ Bicarbonate =< 15 mEq/L ❑ Bicarbonate > 15 mEq/L
❑ Moderate ketonuria or ketonemia ❑ Minimal ketonuria and
ketonemia

Kitabchi AE. Hyperglycemic Crises in Adult Patients With Diabetes. Diabetes Care. Jul 2009; 32(7): 1335-1343

7/15/2020 Vy Vu
DKA/HHS – MAGEMENT

7/15/2020 Figure 5: DKA/HHS Management

Kitabchi AE. Hyperglycemic Crises in Adult Patients With Diabetes. Diabetes Care. Jul 2009; 32(7): 1335-1343
CHRONIC COMPLICATIONS

7/15/2020 Vy Vu
DIABETES COMPLICATIONS
Microvascular Macrovascular
Diabetic Retinopathy Atherosclerosis Cardiovascular
Diabetic Kidney Disease Disease (ASCVD)
Diabetic Neuropathy Stroke
MI

Reduce risk of microvascular and macrovascular complications!

7/15/2020 Vy Vu
MICROVASCULAR - DIABETIC NEPHROPATHY
(DIABETIC KIDNEY DISEASE)
❑ Chronic kidney disease (CKD)
▪ Increased urinary albumin excretion (albuminuria) and
▪ Low estimated glomerular filtration rate (eGFR) =< 60 ml/min

❑ Damaged glomeruli are unable to reabsorb protein

due to high permeability

❑ Screening of urinary albumin to creatinine ratio

(UACR) and eGFR annually

7/15/2020 Vy Vu
MICROVASCULAR - DIABETIC NEPHROPATHY

Category UACR

Normal <30 mg/g

Albuminuria ≥30 mg/g

7/15/2020 Vy Vu
MICROVASCULAR - DIABETIC RETINOPATHY
❑ Increased risk with
▪ Duration of diabetes
▪ Low level of glycemic control
▪ Nephropathy
▪ Hypertension
▪ Dyslipidemia
❑ Screening
▪ Type 1: within 5 years of diagnosis
▪ Type 2: at the time of diagnosis
▪ If no evidence of retinopathy: 1-2 years

7/15/2020 Vy Vu
MICROVASCULAR - DIABETIC NEUROPATHY
❑ Diabetic peripheral Neuropathy (DPN)
▪ Unpleasant sensations of burning and tingling
▪ Numbness and loss of protection sensation (POPS)
▪ Other causes should be considered: alcohol, B12 deficiency,
hypothyroidism, renal disease, malignancy, infections.
❑ Treatment
▪ Improved glycemic control
▪ FDA approved drugs: Pregabalin, Duloxetine

7/15/2020 Vy Vu
MICROVASCULAR - DIABETIC NEUROPATHY
❑ Diabetic Autonomic Neuropathy
▪ Hypoglycemia unawareness
▪ Resting tachycardia
▪ Orthostatic hypotension
▪ Gastroparesis, constipation, diarrhea
▪ Erectile dysfunction/retro grade ejaculation
▪ Bladder dysfunction
▪ Increase/decrease sweating
▪ Neuropathic pain
❑ Treatment of Gastroparesis
▪ FDA approved agent: Metoclopramide

7/15/2020 Vy Vu
MICROVASCULAR – DIABETIC NEUROPATHY
❑ Foot ulceration and amputation are the major cause of
morbidity/disability

❑ Screening
▪ Annual comprehensive foot care
▪ Feet inspection at each visit
▪ Neurologic exam

7/15/2020 Vy Vu
MACROVASCULAR – CARDIOVASCULAR DISEASE
❑ Definition
▪ Atherosclerosis the blood vessels provide circulation to the brain, heart, and
extremities

❑ Result in
▪ Stroke
▪ MI
▪ Peripheral arterial disease

7/15/2020 Vy Vu
ASCVD CALCULATOR
❖ American College of Cardiology/American Heart Association ASCVD
risk calculator: tool to calculate risk.

7/15/2020 Vy Vu
ASCVD RISK CALCULATOR

7/15/2020 Vy Vu
MANAGEMENT AND PREVENTION
MACROVASCULAR COMPLICATIONS
❑ Hypertension
▪ BP <140/90
▪ BP <130/80
❑ Dyslipidemia
▪ Moderate intensity statin
▪ High intensity statin
❑ Coronary Artery Disease (CAD)
❑ Antiplatelet therapy: ≥ 50 yo with one additional risk factor
▪ Aspirin (75-162 mg/day)/Clopidogrel ( 75mg/day)
❑ Smoking Cessation

7/15/2020 Vy Vu
STATIN INTENSITY

7/15/2020 Vy Vu
CORONARY HEART DISEASE
❑ Routine screening not recommended in asymptomatic patients

❑ Consider investigations for CAD in the presence of

▪ Atypical cardiac symptoms (eg unexplained dyspnea, chest discomfort)
▪ Signs/symptoms of vascular disease (TIA, stroke, PAD, claudication, EKG
abnormality, carotid bruits)

7/15/2020 Vy Vu
COMPREHENSIVE MEDICAL CARE

Figure: Decision cycle for patient-centered glycemic management in type 2 diabetes

ADA Comprehensive Medical Evaluation and Assessment of Comorbidities. Diabetic Care, volume 43, supplement 1 2020 .
7/15/2020 Vy Vu
COMPREHENSIVE DIABETES CARE

Figure 2: Components of comprehensive diabetes care

Goodman and Gilman. The Pharmacological Basic of Therapeutic,13E 2017
7/15/2020 Vy Vu
GOALS OF THERAPY
❑ Alleviate of hyperglycemia
❑ Prevent/Reduce the risk of acute metabolic decompensation
❑ Prevent/Reduce the risk of chronic end-organ complications

7/15/2020 Vy Vu
SETTING GLYCEMIC GOALS
GLYCEMIC PARAMETERS GOALS ACCORDING TO ADA GUIDELINES

A1C < 7%

PREPRANDIAL 80-130 mg/dL

POSTPRANDIAL < 180 mg/dL (1-2h after the beginning of the meal)

7/15/2020 Vy Vu
SETTING GLYCEMIC GOALS
❑ A reasonable goal for many adults is A1C <7%

❑ More stringent: A1C <6.5%: short duration of diabetes, DM2

patients who are only treated with lifestyle modifications or
metformin, long life expectancy, and no significant CVD

❑ Less stringent: A1c <8%: history of severe hypoglycemia, limited

life expectancy, advanced microvascular or macrovascular
complications, and comorbid conditions, longstanding diabetes in
whom the general goal is difficult to achieve.

7/15/2020 Vy Vu
NON-PHARMACOLOGIC THERAPY
❑ Diabetes Prevention Program (DPP): 7% weight loss
❑ Moderate-intensity activity: 150 min/week
❑ Smoking cessation
❑ In type 1 diabetes: matching calories intake and insulin dose

7/15/2020 Vy Vu
PHARMACOLOGIC TREATMENT - OVERVIEW

7/15/2020 Vy Vu
PHARMACOLOGIC TREATMENT - OVERVIEW

Glucagon-like
peptide receptor
agonists (GLP-1
agonists)

7/15/2020 Vy Vu
ANTIDIABETIC DRUG – GROUP PRESENTATION
• Mechanism of action
• Route of administration
• Pharmacology
• Indications
• Contraindications
• Side effects
• Drug interactions

7/15/2020 Vy Vu