Managing Diabetes Mellitus

By Karina Bonitto and Jenifer DeNormandie

Learning Objectives

⦿Review the pathophysiology of Diabetes and how it relates to therapy⦿Summarize available treatment options

for diabetes mellitus ⦿Describe different methods of glucose

logging to meet the needs of patients⦿Recall techniques to help patients be

more comfortable with injectable therapy

Road Map

⦿Today●Epidemiology●Pathophysiology●Types of diabetes●Treatment options

○ Oral agents○ Injectable therapy○ Side effects

●Guidelines●Carb counting●Home monitoring●Smart phone Apps●Cases

⦿Next week● Complications● Microvascular

○ Eye Disease○ Neuropathy○ Nephropathy

● Macrovascular○ CHD○ PAD○ CVD

● Other

Epidemiology: The Diabetes Epidemic: Global Projections 2010–2030

IDF. Diabetes Atlas 5th Ed. 2011

Pathophysiology⦿Diabetes is a group of metabolic disorders that

results in hyperglycemia and metabolism abnormalities

Classification

⦿Type 1⦿Type 2⦿Gestational⦿Drug induced

Type 1 (Insulin dependent)⦿Usually in young adults and adolescents

●Can present at any age●Ketoacidosis is more common

⦿Total insulin deficiency which is often due to beta cell destruction.●immune mediated

○ macrophages and T lymphocytes with autoantibodies to beta cell antigens⦿Typical presentation: polyuria, polydipsia,

nausea, blurred vision due to hyperglycemia

Diabetic Ketoacidosis⦿Caused by increased fatty acid metabolism

and accumulation of ketoacids ⦿ Triggered by infections and problems with insulin therapy⦿Can be fatal⦿Symptoms can develop quickly● Polydipsia, SOB, confusion, fatigue, n/v,

frequent urination, fruity scented breath⦿ Labs: hyperglycemia, anion gap acidosis, ketonuria or ketonemia⦿ Treatment: IV regular insulin, fluid resuscitation

Type 2 (Non-insulin dependent) ⦿Majority of diabetes cases (90-95%)⦿Insulin resistance and progressively lowering

insulin secretion● Insulin resistance often manifests as increased

lipolysis and free fatty acid production, increased hepatic glucose production, and decreased glucose uptake by skeletal muscle⦿Abdominal obesity

⦿Co-morbidities often present⦿Typical presentation: retinopathy, neuropathy,

nephropathy, obesity, HTN

Type 1 Vs Type 2Type 1 Type 2

Etiology Autoimmune Insulin resistance

Age of Onset Younger Older

Family History Rare Common

Obesity Rare Common

Insulin Resistance No Yes

Ketosis Yes No

Genetic association (HLA)

Yes No

Insulin presence within the body

No Yes

Response to oral agents

No Yes

Gestational Diabetes Mellitus

⦿Hormonal changes result in insulin resistance⦿New onset glucose intolerance during

pregnancy⦿Usually presents in third trimester

Drug Induced Diabetes⦿Pentamidine⦿Glucocorticoids⦿Atypical antipsychotics⦿Protease inhibitors⦿Hydrochlorothiazide⦿Diazoxide⦿Interferon (alpha)⦿Nicotinic acid

Diagnosis

⦿Any of the following:●A1C ≥ 6.5%●Fasting plasma glucose (FPG) ≥126 mg/dL●2 hour OGTT ≥ 200 mg/dL●Random plasma glucose ≥ 200 mg/dL

Pharmacologic Treatment⦿Metformin⦿Insulin

secretagogues⦿Thiazolidinediones⦿Alpha-GI⦿DPP-4 inhibitors⦿GLP-1 RA⦿Amylin analogs⦿Bile Acid

sequestrants

⦿DA agonists⦿SGLT-2 inhibitors⦿Insulins

●Rapid●Short●Intermediate●Long

Goals of Treatment

⦿Reduce the risk of microvascular and macrovascular complications⦿Ameliorate symptoms⦿Reduce mortality⦿Improve QOL

Treatment Options: Metformin⦿Gold standard⦿Enhances insulin sensitivity of hepatic and

peripheral tissues⦿BBW: Lactic acidosis⦿Contraindicated if SCr ≥1.5 or ≥1.4 (f)⦿Dosing

●IR: 500mg BID with food●ER: 500mg 1 QD with evening meal●Max: 2500mg daily

Treatment Options: Insulin Secretagogues⦿Stimulate insulin secretion from beta-cells⦿Maximal glycemic control at 6 months⦿Contraindicated in T1DM, DKA, concurrent used

with bosentan (glyburide) or gemfibrozil (repaglinide)⦿Dosing

●Glyburide 2.5-5 mg/day●Glipizide 5 mg/day●Glimepiride 1-2 mg/day●Nateglinide 120 mg TID●Repaglinide 0.5-2 mg before each meal dependent on

HbA1C

Treatment Options: Thiazolidinediones (TZDs)⦿Similar efficacy with glycemic control⦿Pioglitazone reduces mortality, MI, and stroke

in high risk patients⦿BBW: CHF⦿Contraindicated in CHF and pulmonary

edema⦿Dosing

●Pioglitazone 15 or 30 mg QD●Rosiglitazone 4 mg/day

Treatment Options: Alpha-GI⦿Delays and reduces post-meal carbohydrate

absorption and postprandial blood glucose⦿Contraindicated in IBD, intestinal obstruction,

malabsorption, cirrhosis, and CrCl< 25mL/min or SCr>2mg/dL⦿Dosing

●Arcarbose (Precose): 25mg with the first bite of meal once a day then increase weekly to 2 times/day then 3 times/day

●Miglitol (Glyset): 25 mg with the first bite of meal

Treatment Options: DPP-4 Inhibitors⦿Increases insulin secretion from beta-cells

and decreases glucagon secretion from alpha-cells⦿Caution: Acute pancreatitis, joint pain,

hepatotoxicity (alogliptin)⦿Dosing

●Sitagliptin 100 mg QD●Saxagliptin 2.5-5 mg QD●Linagliptin 5 mg QD●Alogliptin 25 mg QD

Treatment Options: GLP-1 RA⦿ Increases insulin secretion, decreases

glucagon secretion and slows gastric emptying

⦿BBW: Thyroid C-cell tumor risk (excludes exenatide IR)

⦿Dosing● Exenatide IR: 5 mcg SC BID x 1 month then

10 mcg SC BID (1 hour before meals)● Exenatide ER: 2 mg SC Weekly● Liraglutide: 0.6 mg SC QD x 1 week , then 1.2

mg SC QD● Dulaglutide: 0.75 mg SC Weekly● Abiglutide: 30 mg SC Weekly

Treatment Options: Amylin Analogs⦿Slows gastric emptying and suppresses

postprandial glucose⦿BBW: Co-administration with insulin increases

the risk of hypoglycemia⦿Contraindications: gastroparesis,

hypoglycemic unawareness⦿Reduce mealtime insulin by 50%⦿Dosing

●Type 1: Pramlintide 15 mcg before meals●Type 2: Pramlintide 60 mcg before meals

Treatment Options: Bile Acid Sequestrants⦿Binds bile acids and decreases hepatic

glucose production⦿Contraindicated with bowel obstruction,

triglycerides > 500 mg/dL, or history of hypertriglyceridemia-induced pancreatitis⦿Dosing

●Colesevelam (Welchol): 3 x 625 mg tabs twice daily or 6 tabs daily with meals

●Suspension: 3.75 g/packet once daily with largest meal

Treatment Options: DA Agonists⦿Activates the DA receptor and modulates

hypothalamic control of metabolism●Does not increase plasma insulin, but rather it

decreases insulin resistance⦿Contraindicated with lactation, syncopal

migraines, or hypersensitivity to ergot derivatives or dopamine⦿Dosing

●Bromocriptine (Cycloset): 0.8mg w/in 2 hours of waking in the morning with food; titrate to 0.8 mg/week to a mean daily dose of 4.8 mg every morning

Treatment Options: SGLT-2 inhibitors⦿Lowers the renal threshold and reduces

reabsorption of glucose⦿Contraindicated in CrCl <30mL/min, ESRD,

dialysis⦿Glucosuria can increase risk of UTI and

urinary frequency, risk for ketoacidosis⦿Dosing

●Canagliflozin 100 mg QD before breakfast●Dapagliflozin 5 mg QAM●Empagliflozin 10 mg QAM

Treatment Options: Insulins⦿Rapid

●Novolog, Humalog, Apidra (glulisine)⦿Short

●Humulin R, Novolin R⦿Intermediate

●Novolin N, Humulin N, NPH⦿Long

●Levemir, Lantus (detemir), Tresiba (degludec), Toujeo (glargine)

Treatment Options: Side Effects Met GLP1

RASGLT2i

DPP-4i

AGi TZD SU/Meg

Colsvl BCR Ins Praml

Hypo mild-sev

mod-sev

Weight loss loss loss gain gain gain loss

Renal/GU

GI mod mod mod mild mod

CHF mod

Bone Fracture Risk

Guidelines: AACE v ADA

⦿There is extensive overlap between the two⦿Key differences:

Biochemical Index ACE/AACE ADA

A1C ≤6.5% ≤7%

Preprandial plasma glucose

70-130 mg/dL <110 mg/dL

Postprandial plasma glucose

<180 mg/dL <140 mg/dL

Guidelines

Carb Counting⦿Meal planning technique to manage blood

glucose levels⦿Amount of carbohydrates consumed is

dependent on the individual⦿ADA recommends starting at 45-60 grams of

carbohydrates at a meal⦿Please see handouts for easy carb counting

for patients

Home Monitoring

⦿How to on testing blood sugars⦿Different monitoring systems⦿Frequency of monitoring

Smart Phone Apps⦿Various ones available for free

●Glooko: for iPhone and Android○ Sync and log blood sugar levels with

doctor’s devices. FDA approved as Class II clinical device. The app is free, subscription required

●Diabetes logbook: for iPhone and Android○ Gamified logbook

●Diabetik: for iPhone○ Simple basic design that allows users to set

medication and appointments reminders based on preset information and location

Think, Pair, Share: Case 1

HL is a 56 y/o obese female with a family history significant for diabetes and presents for her annual physical exam. A FPG is 170 mg/dL and she has no concerns to discuss. How should HL be managed?

A.Reassess in 1 year at her next physicalB.Obtain a f/u FPG in 1 weekC.Diagnose type 2 DM and discuss

dietary and lifestyle changes

Think, Pair, Share: Case 2

AR is a 46 y/o male newly diagnosed with type 2 diabetes last month. He has a BMI of 34kg/m2 and his most recent A1C was 8.5% and has normal renal function. His FPG readings ranged from 150-180 mg/dL despite his efforts to implement dietary changes and starting to exercise more frequently.

Think, Pair, Share: Case 2

Which option is best for AR?

A.Continue with diet and exercise for 1 year before trying pharmacologic treatment

B.Start metformin 500 mg twice daily titrating up to 2000 mg/day

C.Start basal insulin as his A1C indicates need for insulin therapy

D.Start glyburide 10 mg twice daily

Overcoming obstacles with injectable therapyhttp://mediacenter.novomedlink.com/v/injectables-in-the-treatment-of-type-2-diabetes-a-guide-to-overcoming-patient-concerns?utm_source=nni%20media%20center&utm_medium=email&utm_content=unbranded&utm_campaign=share

References⦿ https://www.aace.com/sites/all/files/diabetes-algorithm-executive-summary.pdf⦿ http://accesspharmacy.mhmedical.com.une.idm.oclc.org/content.aspx?

bookid=689&Sectionid=45310509.⦿ http://www.clinicalpharmacology-ip.com.une.idm.oclc.org/Forms/Resources/overviews.aspx⦿ http://www.nature.com/nrd/collections/type2diabetes/sponsors/index.html⦿ http://www.diabetes.org/food-and-fitness/food/what-can-i-eat/understanding-carbohydrates/carbohydrate-counting.html⦿ http://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0024704/⦿ http://www.mayoclinic.org/diseases-conditions/diabetic-ketoacidosis/basics/definition/con-20026470

⦿ ADA. I. Classification and Diagnosis. Diabetes Care 2011;34(suppl 1):S13. Table 2