DIABETES BOOTCAMP 2016 · Test for GDM at 24 -28 weeks of gestation in women not previously ... hypoglycemia, use insulin analogs 4. For patients with frequent nocturnal hypoglycemia,

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DIABETES BOOTCAMP 2016In other words: Everything you want to know about Treating Diabetes

DISCLOSURES:

Sanofi: paid consultant and speaker

Boehringer Ingerheim: paid consultant and speaker

Janssen/Healthscripts: paid consultant and speaker

OBJECTIVES

• Section 1:• Prevalence DM: Worldwide,US/ Oklahoma• Characteristics of T1, T1.5, T2, MODY, GEST DM• Causative factors of differing types DM and prevalence worldwide,

nationally, locally• Other types DM: pathology and prevalence• Diagnosing DM: T1, T1.5, T2, Gestational DM

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OBJECTIVES

• Section 2:• Identify treatment options for DM: lifestyle changes, non-insulin

injectable and insulin• Pharmokinetics and pharmodynamic effects of oral agents used in

DM, of non-insulin injectables and insulins• Most common adverse effects of oral agents, non-insulin injectibles

and insulins used in treatment of DM• Treatment of hypoglycemia

DEFINING DIABETESRefers to a group of common metabolic disorders that share the phenotype of hyperglycemiaJameson, 2013

PREVALENCE OF DIABETES

1. Worldwide2. United States3. Sooner State

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EPIDEMIOLOGY OF DIABETES

�29.1 million Americans, 9.3% of the population, have diabetes� Diagnosed: 21.0 million� Undiagnosed: 8.1 million

�1.25 million have type 1 diabetes� Leading cause of kidney failure, nontraumatic

lower-limb amputation, new cases of blindness among adults

�Major cause of heart disease and stroke�Seventh leading cause of death

National Diabetes Information Clearinghouse. National Diabetes Statistics, 2014. Available at: http://diabetes.niddk.nih.gov/dm/pubs/statistics/

Age-adjusted Prevalence of Obesity and Diagnosed Diabetes Among US Adults

Obesity (BMI ≥30 kg/m2)

Diabetes

1994

1994

2000

2000

No Data <14.0% 14.0%–17.9% 18.0%–21.9% 22.0%–25.9% > 26.0%

No Data <4.5% 4.5%–5.9% 6.0%–7.4% 7.5%–8.9% >9.0%

CDC’s Division of Diabetes Translation. United States Diabetes Surveillance System available at http://www.cdc.gov/diabetes/data

2014

2014

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PREVALENCE OF DM IN SOONER STATE

• The number of Oklahomans living with Diabetes has grown steadily over the last 10 years (2012)

• In 2012, 11.5% of all Oklahomans were diagnosed with Diabetes. • Oklahoma ranked 9th highest in nation for prevalence of people

living with Diabetes

•

DIABETES MELLITUSRefers to a group of common metabolic disorders which share the phenotype of hyperglycemiaTwo most common categories of Diabetes are T1 and T2 diabetes (T1DM and T2DM, respectively)• T1DM: complete or near complete insulin deficiency• T2DM: variable degrees of insulin resistance, impaired insulin

secretion and increased glucose production• T1.5: Latent auto immune diabetes in Adults: progression of

autoimmune B-cell failure is slow despite islet cell antibodies present.

• Gestational Diabetes (GDM): Glucose intolerance which develops during pregnancy due to insulin resistance related to metabolic changes of late pregnancy and increased insulin requirements.

• MODY: Maturity Onset of Diabetes of the Young, subtype DM with autosomal dominant inheritance, onset age typically <25 years, hyperglycemia with impairment of insulin secretion.

TYPE 1 DIABETESResult of:1. Genetic factors2. Environmental factors3. Immunologic factors

Equals pancreatic beta cell destruction and insulin deficiencyMajority of patients with T1DM have evidence of islet directed autoimmunityIf beta cell destruction and insulin deficiency is abrupt, these patients may present in DKA.May have “honeymoon” period shortly after diagnosis when glycemic control is achieved with modest doses of exogenous insulin (endogenous insulin fromremainingbeta cells)

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T2DMCauses

Prevalence

T1.5 DIABETESCauses

prevalence

OTHER TYPES DIABETESCauses

prevalence

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DIAGNOSING DIABETES

CRITERIA FOR DIAGNOSING DM

� Fasting plasma glucose >126 mg/dlOR� 2hr plasma glucose >200 mg/dl during an OGTTOR

� A1C >6.5% OR� Random plasma glucose >200mg/dlAmerican Diabetes Association Standards of Care, Classification of diabetes. Diabetes Care 2016; 39 (Suppl 1) S13-S22

FASTING PLASMA GLUCOSE AND 2 HROGTT

� Fasting plasma glucose =/>126 mg/dl*OR� 2hr plasma glucose =/>200mg/dl during an OGTT*

*In the absence of unequivocal hyperglycemia, result should be confirmed by repeat testing

American Diabetes Standards of Medical Care in Diabetes. Classification and diagnosis of diabetes. Diabetes Care 2016; 39 (Suppl1) S13-S22

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RECOMMENDATIONS FOR SCREENING FOR TYPE 1 DM

� Blood glucose rather than A1C should be used to diagnose T1DM in symptomatic individuals

� Inform relative of patients with T1DM of the opportunity to be test for the T1 diabetes risk, but only in the setting of a clinical research study (diabetestrialnet.org)

RECOMMENDATIONS: DETECTION AND DIAGNOSIS OF GDM

� Test for undiagnosed T2DM at the first prenatal visit in those with risk factors

� Test for GDM at 24-28 weeks of gestation in women not previously known to have diabetes

� Screen women with GDM for persistant diabetes at 6-12 weeks postpartum, using OGTT

American Diabetes Association Standards of Medical Care in Diabetes. Classification and diagnosis of diabetes. Diabetes Care 2016; 39 (Suppl 1) S13-S22

RECOMMENDATIONS: DETECTION AND DIAGNOSIS GDM

� Women with GDM history should have lifelong screening for development of diabetes or prediabetes at least every 3 years

� Women with GDM history found to have prediabetes should receive lifestyle interventions or metformin to prevent diabetes

American Diabetes Association Standards of Medical Care in Diabetes. Classification and diagnosis of diabetes. Diabetes Care 2016; 39 (Suppl 1) S13-S22

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QUESTIONS?

SECTION TWO

Lifestyle ModificationsOral antihyperglycemicsInjectible Non-InsulinsInsulin

Case Presentations

NOBEL PRIZE In 1923 the Nobel Prize in Medicine was awarded to J.J.R. Macleod, head of Physiology at the University of Toronto and Frederick Banting, a young Ontario orthopedic surgeon for the discovery of insulin

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A1CLowering A1C to <7% has been shown to reduce microvascular complications and, if implemented soon after the diagnosis of diabetes, is associated with long-term reduction in macrovascular disease.

Consider more stringent goals (e.g. <6.5%) for select patients if achievable without significant hypos or other adverse effects.

Consider less stringent goals (e.g. <8%) for patients with a hx of severe hypoglycemia, limited life expectancy, or other conditions that make <7% difficult to attain.

LIFESTYLE MODIFICATION:PHYSICAL ACTIVITYc Adults with diabetes should be advised

to perform at least 150 min/

week of moderate-intensity aerobic

physical activity (50–70% of maximumheart

rate), spread over at least

3 days/week with no more than 2

consecutive days without exercise. A

c All individuals, including those with

diabetes, should be encouraged to

reduce sedentary time, particularly

by breaking up extended amounts

of time (.90 min) spent sitting. B

c In the absence of contraindications,

adults with type 2 diabetes should be

encouraged to perform resistance

training at least twice per week. A

NUTRITION

Dietary interventions are critical in Diabetes. While healthy eating can decrease insulin needs for persons with T1DM, it is VITAL for persons living with T2DM.

Refer each and every patient for DSME.

This can be done at initial dx, yearly and with any transition or change in care.

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APPROACHES TO GLYCEMIC CONTROL WITH MEDICATIONS:ORAL ANTIHYPERGLYCEMICS

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T2DM GUIDELINES: METFORMIN

Ø LIFESTYLE MODIFICATIONS: encourage 150 minutes of physical activity, 7% loss ow exces body weight, healthy eating (less processed foods)

Ø ADD METFORMIN, if not contraindicated and if tolerated is preferred initial pharmacological agent for T2DM.

Ø Metformin is a sensitizer, which means it will help patients use his/her insulin more efficienty

Ø Use eGFR to dose metformin in your patient. Can be used to an GFR of 30, although must be cautious as there is rare risk of lactic acidosis. Obtain Egfrprior to initiation of metformin.

Ø According to FDA Warning issued in April 2016, starting metformin in patients with eGFR between 30-45 is not recommended and contraindicated in patients with eGFR <30

Ø Side effects: Diarrhea. Use of extended release formulation will help most times.

Ø Also encourage patient to take metformin AFTER eating meals.

Ø If not tolerated, or if contraindicated, may use another first line medication: SGLT2 inhibitor, GLP1 agonist, etc. (moving down lost of AACE guidelines)

GLP1 AGONISTS

Ø Incretin therapy, has biologic effects: slows food absorption which then allows the slower insulin response found in persons with T2 diabetes to “catch up”.

Ø Also improves insulin productionØ Decreases the excessive release of

glucagonØ Byetta was first glucagon like peptide

1 agonist (GLP1 agonist)to market in 2005, dosed BID AC by SC injection

Ø All GLP1 agonists are by SC injection

� Weight negative, most patients will lose some weight with these medications as they increase satiety with meals.

� Come with black box warning: medullary thyroid CA. Ask about family hx. Discuss black box warning with patient

� Contraindicated in patients with hx of recurrent pancreatitis. Unknown correlation.

GLP1 AGONISTS: NONINSULIN INJECTABLES

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SGLT2 INHIBITORS

� Canagliflozin� c Dapagliflozin� c Empagliflozin

� Inhibit SGLT2 in the proximal nephron

� Thereby blocking glucose reabsorption increasing glucosuria

� Benefits: hypoglycemia risk is low, weight negative, slightly lowers systolic b/p, effective throughout all stages of T2DM, EMPA-REG study reflected lowered CVD event rate and mortality

� a/e: genital mycotic infections, UTI, fluid shift/hyovolemia, transient egfrdecrease/ scr increase, LDL increase, DKA

DPP4 INHIBITORS: ORAL INCRETIN THERAPIES

� Sitagliptin� Saxagliptin� Linagliptin� Alogliptin

� Inhibit DPP4 activity, increasing PP active incretin (GLP1 and GIP) concentration

� Increase insulin secretion(glucose dependent)

� Decrease glucagon secretion� Benefits: hypo risk is low and well

tolerated. Weight neutral� A/e: angioedema. Contraindicated

in patients with recurrent pancreatitis.

TZD: PIOGLITAZONE

� Pioglitazone

� Activates the nuclear transcription factor PDAR-Y. May take 4-6 weeks to lower blood sugar when initiating. Also will take 4-6 weeks once d/c to notice blood sugar effect (caution patient)

� Sensitizer� Benefits: Hypo risk is low, increases

HDL, lowers trigs, ? Lowers CVD events� A/E: weight positive:especially if used

in conjuction with insulin, increase edema, HF, bone fx risk

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BILE ACID SEQUESTRANT(S)

� Colesevelam

� Binds bile acids in intestine� ? Decreases hepatic glucose

production� ? Increase incretin levels� Benefits: decrease LDL-c, hypo risk is

low. � A/E: may cause constipation, ,ay

increase trigs, may decrease absorption of other meds

BROMOCRIPTINE QR

� Bromocriptine QR (Cycloset)

� Activates dopaminergic receptors� Modulates hypothalamic regulation

of metabolism� Benefits: hypo risk low, ? Lowers

CVD events.

� A/E: dizziness/syncope, Nausea, fatigue, rhinitis.

AGI: A- GLUCOSIDASE INHIBITOR(S)

� AGI: acarbose

� Inhibit intestinal a-glucosidase � Slows intestinal CHO absorption� Benefits: hypo risk is low, decreases

pp glucose excursions, non-systemic� A/E: flatulence, diarrhea, frequent

dosing schedule

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SULFONYLUREAS

� 2nd Generation:� Glyburide

� Glipizide

� Glimepiride

� Increase insulin secretion� Benefits: decrease microvascular

risk ( UKPDS)� A/E: HYPOGLYCEMIA, weight gain,

lose efficacy over time

QUESTIONS?

INSULINTypesHow to Initiate in Patients with T1/T2DM

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INSULIN(S)

Rapid, Short and Intermediate

Rapid: lispro, aspart, glulisine, inhaledShort acting: human regularIntermediate acting: human NPH

Basal� Glargine: u100 and u300. U300 half life is 19 hours.

Steady state in 4-5 days once initiated. Benefit: U300 less variability when compared to u100 glargine due to flat pharmokinetic profile. Ultra-long duration of action >30 hours

� Determir: u100� Degludec: u100 and u200. Half life is 25 hours, reaches

steady state in 3 days once initiated. Benefit: less variability of blood sugars when compated to glargine u100 due to flat pharmokinetic profile. Ultra-long duration of action >42 hours

� Premixed: several types� Concentrated Regular: u-500. Half life is 4 hours,

duration of action is 6-10 hours.

INSULIN: T1 AND T1.5 DIABETES

1. Multiple daily dose therapy: basal/bolus insulin is best2. Match prandial insulin to CHO intake, premeal glucose, and

anticipated glucose activity3. For most patients, and especially for those at risk of

hypoglycemia, use insulin analogs

4. For patients with frequent nocturnal hypoglycemia, recurrent severe hypoglycemia and/or hypoglycemia unawareness, a sensor augmented pump may be considered

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CASE PRESENTATIONS

CASE PRESENTATION(S)