Endo E1- T2DM

In T2DM, is lack of endogenous insulin relative or absolute?

Relative

What usually causes relative insulin deficiency?

resistance to the actions of insulin in muscle, fat, and liver AND inadequate response by the pancreatic beta cell

What is insulin resistance attributed to?

dec glucose transport in muscle

elevated hepatic glucose production

inc breakdown of fat

What 4 things contribute to inc BG?

carb intake, dec peripheral glucose uptake, dec insulin secretion, inc hepatic glucose production

Is hyperglycemia more related to microvascular or macrovascular disease?

Microvascular

When does the “clock start ticking” for microvascular risk?

onset of hyperglycemia

When does the “clock start ticking” for macrovascular risk?

onset of insulin resistance

In the US, DM is most prevalent in what race?

American Indians & Alaska natives

What do ~ 2/3 of people with diabetes die from?

heart disease or stroke

How much does DM inc the risk for coronary artery disease?

Women: 3-4 fold inc

Men: 2 fold inc

At what age should testing for prediabetes begin?

45

When should testing for prediabetes be considered in asymptomatic adults (at any age)?

with BMI ≥ 25 who have 1+ risk factors

*23 in Asian Americans

If screening tests for prediabetes are normal, how often should tests be repeated?

Every 3 years

When should prediabetes testing be considered in children & adolescents?

overweight/obese with 2+ additional risk factors

What is the best screening method for T2DM?

FPG, OGTT, and A1C

*all equally appropriate

What is the criteria for prediabetes?

FPG: 100-125

2h plasma glucose: 140-199

A1C: 5.7-6.4%

If a child/adolescent is overweight and has 2 additional risk factors, when should testing for DM be initiated? How frequently should they be tested?

Age 10, every 3 years

What are sx of hyperglycemia?

blurred vision, LE paresthesias, yeast infections

What are possible PE findings w/ DM?

central obesity, HTN, acanthosis nigricans, candida infxn, dry feet, claw toes, eye hemorrhages/exudates, dec sensation, loss of DTRs

Which tube is used to determine plasma glucose & inhibits red blood cell glyocolysis immediately?

Gray

Which tube is used to determine serum glucose?

Red/speckled

Criteria for diagnosis of T2DM

A1C ≥ 6.5%

FPG ≥ 126 mg/dl

OGTT ≥ 200 mg/dl

OR in a pt with classic symptoms, random plasma glucose ≥ 200 mg/dl

What urine levels are recommended for yearly screening in all patients with diabetes?

Microalbumin

*normal (< 30)

If urine microalbumin levels are abnormal (>30), what additional test should be performed?

timed urine specimen

How is persistent microalbuminuria confirmed?

(+) 2/3 samples over 3-6 months

Are antibodies to insulin, islet cells, or GAD present in T2DM?

No

What is the foundation of treatment program for T2DM?

Diet, Exercise, Education

What is the optimal first line drug for treatment of T2DM?

Metformin

After metformin, what is added to control BG?

1-2 additional oral or injectable agents

What is the last line of tx for T2DM?

insulin therapy (alone or in combo)

When treating T2DM, how is microvascular risk reduced?

Control of glycemia & BP

When treating T2DM, how is macrovascular risk reduced?

Control of lipids, HTN, smoking cessation, & ASA therapy

When treating T2DM, how is metabolic risk reduced?

Control of glycemia

How often should an A1C test be performed in patients who meet treatment goals and have stable glycemic control?

2x anually

How often should an A1C test be performed in patients whose therapy has changed or who are not meeting glycemic goals?

Quarterly

At what A1C should you start thinking about insulin therapy?

9%

What are the gylcemic recommendations for non-pregnant adults with diabetes?

A1C: <7%

preprandial plasma glucose: 80-150

postprandial plasma glucose: <180

Reducing HbA1C by 1% can have what effects?

Decreases diabetes-related deaths, MI, and microvascular complications

When is daily SMBG recommended for pts w/ T2DM?

pts that are treated w/ insulin or insulin secretagogues to prevent hypoglycemia

Do pts managing their DM w/ lifestyle changes or non-hypoglycemic agents require SMBG?

No

When should SMBG be taken?

prior to meals and snacks, bedtime, prior to exercise, low BG, prior to critical tasks (driving)

When it comes to diet modifications what is most importance?

Caloric restriction

What is considered a low and high glycemic index?

< 55

> 70

In T2DM patients, what increases insulin response without raising plasma glucose concentrations?

Protein

T/F: Carb sources that are high in protein are ideal for treating hypoglycemia

FALSE- protein increases insulin response

What do Omega-3 fatty acids help to prevent/treat?

CVD

Does alcohol consumption put diabetic patients at risk for hyperglycemia or hypoglycemia?

Hypoglycemia

What should sodium be restricted to for pts w/ DM?

< 2,300 mg/day

Which diet is more beneficial in managing T2DM?

Mediterranean (< 50% cal from carbs); showed more wt loss and glycemic control than low-fat diet

What patients should have a CV evaluation with imaging prior to beginning an exercise regimen?

Older pts, Pts with long-standing disease, Pt with multiple risk factors, Pts with evidence of atherosclerotic disease

What is the exercise recommendation for children with diabetes or prediabetes?

60 min/day physical activity

What is the exercise recommendation for adults with T1DM or T2DM?

150+ min/week of moderate-vigorous exercise over at least 3 days, with no more than 2 consecutive days without exercise

How often per week should adults with T1DM or T2DM perform resistance training?

2-3 sessions/week on nonconsecutive days

In diabetic patients, how often should prolonged sitting be interrupted for BG benefits?

every 30 minutes

Normal BMI:

<25

Overweight BMI:

25-29.9

Obese BMI:

30.0-39.9

What T2DM patients are good candidates for metabolic surgery?

BMI >40, or BMI 30-39.9 with uncontrolled hyperglycemia despite optimal medical control

Pts who are symptomatic at presentation may require what tx?

insulin or insulin secretagogue to rapidly relieve glucose toxicity & sx

Which pts are usually treated initially with single oral agents?

pts w/ A1C <7.5%

Which pts may benefit from initial therapy with 2 oral agents or insulin?

pts w/ A1C 8-10%

What must be present for biguanides to work?

Insulin

What T2DM drug can cause lactic acidosis?

Metformin

What are contraindications for Metformin?

Renal/Hepatic insufficiency, CHF

How should pts take Metformin?

middle or at the end of meal d/t GI effects

What are some advantages of metformin?

Efficacy, No weight gain or hypoglycemia, Low level of side effects, Cheap, high level of pt acceptance

Which sulfonylurea is a 2nd gen agent that is more potent and exhibits fewer drug interactions than 1st gen agents?

Glyburide

Which sulfonylurea may cause more physiologic insulin release w/ less risk for hypoglycemia and wt gain?

Glipizide

What is the ONLY sulfonylurea approved for concomitant use with metformin or insulin?

Glimepiride (Amaryl)

What sulfonylurea is a 3rd gen and has a safer interaction with cardiac potassium channels compared to the others?

Glimepiride (Amaryl)

Which class tends to be shorter acting & lower risk of hypoglycemia: Meglitinides or Sulfonylureas?

Meglitinides

Which meglitinide is most useful in pts at inc risk for hypoglycemia who still require an insulin secretagogue?

Repaglinide (Prandin)

Which meglitinide mimics endogenous insulin patterns, restores early insulin secretion, and controls mealtime glucose surges?

Nateglinide (Starlix)

Which class of medications prolong the absorption of carbs and have a high degree of GI effects?

alpha-glucosidase inhibitors

*Acarbose (precose)

What drug class reduces insulin resistance in the periphery (muscle/fat)?

Thiazolidinediones (TZDs)

What class of diabetes medications is shown to slow progression of diabetes by preserving beta cell function?

TZDs

What drug class may induce or worsen heart failure?

TZDs

Which TZD improves target cell response to insulin w/o inc insulin secretion AND is more effective at lowering TRG levels?

Pioglitazone (Actos)

Which TZD is an insulin sensitizer w/ major effects on stimulation of glucose uptake in skeletal muscle and adipose tissue, lowering plasma insulin levels BUT has inc CV risk?

Rosiglitazone (Avandia)

What drug class stimulates glucose-dependent insulin release, reduces glucagon, and slows gastric emptying?

Incretin mimetics (GLP-1 agonists)

Which Incretin mimetic has greater ease of titration than insulin, but is more expensive?

Exenatide (Bytetta)

What drug increases intracellular cAMP, leading to insulin release in the presence of elevated glucose?

Liraglutide (Victoza)

Which drugs are long-acting GLP-1 RAs and are given once weekly?

Albiglutide (Tanzeum) & Dulaglutide (Trulicity)

Which drug class degrades numerous biologically active peptides, including GLP-1 and GIP?

DDP-4 inhibitors

Which DDP-4 slows inactivation of incretin hormones thereby increasing and prolonging their action?

Sitagliptin (Januvia)

Which DPP-4 blocks the enzyme DPP-4 thereby inc concentration of active intact incretin hormones, enhancing glycemic control?

Saxagliptin (Onglyza)

What is the role of incretin hormones?

glucose homeostasis: inc insulin release and dec glucagon levels in circulation in a glucose-dependent manner

Which class of drugs inc urinary glucose excretion by lowering the renal glucose threshold?

SGLT-2 inhibitors

Which meds are SGLT-2?

canagliflozin (Invokana), dapagliflozin (Farxiga), empagliflozin (Jardiance)

Which class of drugs delay gastric emptying, dec postprandial glucagon release, and modulate appetite?

Amylin analogues

What drug is an Amylin analogue that promotes satiety leading to dec caloric intake and potential wt loss?

Pramlintide (SymlinPen)

When should you consider insulin therapy as first line?

pts who are markedly symptomatic and/or have BG ≥ 300 or A1C ≥ 10%

What vitamin levels should be measured in patients taking metformin?

B12

When should you add a second oral agent?

noninsulin monotherapy at max dose does not achieve/maitian A1C target over 3 months

What are the ADA recommendations for complications monitoring at time of DM diagnosis?

Yearly dilated eye exams, Yearly microalbumin checks, Foot exams at every visit

Patients who are at high risk for CV events should receive what preventative therapy?

Low dose ASA

What is the BP goal in diabetic patients?

< 140/90

What is the BP goal in diabetic patients with >1 g/d proteinuria and renal insufficiency?

125/75

What is the preferred therapy for patients with HTN? Why?

RAAS inhibitors (ACEi, ARBs), because of renal protection

When is a lipid screen needed in pts w/ DM?

at time of DM diagnosis, an initial medical evaluation, then every 5 years

*also at initiation of statin therapy (if needed)