This lecture is sponsored by a grant from the Delta Dental of Iowa Foundation IDA Annual

Conference Guest Lecture Series.

Diabetes Essentials 2011

Richard LeBlond, MD, MACPChief Quality Officer

Professor, Internal MedicineUniversity of Iowa Health Care

Learning Objectives

• Appreciate the challenge of diabetes from the patient’s perspective

• Differentiate type 1 from type 2• Understand insulin action• Understand complications of diabetes• Know the major classes of medications• Know the side effects of each class• Recognize hypoglycemia as a serious

complication arising during dental care

Diabetes Incidence in Childhood

What is Diabetes?Insufficient insulin activity

• Defined by the blood glucose level• The definition is arbitrary

– Fasting glucose >125 mg/dL– 2 hour post meal glucose > 200 mg/dL– Any glucose > 200 mg/dL– Glycohemoglobin > 6.5%

• Two predominant causes– Decreased insulin levels: type 1– Resistance to insulin action: type 2

Insulin

• Insulin is produced by the beta cells in the islets of the pancreas

• Small amounts of insulin are necessary to sustain life

• Insulin is necessary for the metabolism of carbohydrates

• Insulin acts predominantly on three tissues– Fat cells: take up glucose, convert to fatty acids, and

store energy as triglycerides – Muscle cells: take up glucose and store as glycogen– Liver: take up glucose and store as glycogen; stop

gluconeogenesis (making glucose from amino acids)

Causes of Diabetes

• Type 1: destruction of pancreatic islet cells– Autoimmune, usually childhood onset; genetic

predisposition; probable viral trigger– Non-immune destruction: acute and chronic

pancreatitis; hemochromatosis• Type 2: resistance to insulin action

– Genetic factors– Obesity: decreased adipocyte responsiveness to

insulin– Maturity Onset Diabetes of the Young (MODY):

abnormal insulin signaling– Corticosteroids & stress hormones: cortisol (Cushing

syndrome), growth hormone (acromegaly), epinephrine

Type 1 Diabetes Absolute Insulin Deficiency

• Incompatible with life• Ketoacidosis without insulin• Exogenous insulin is the only treatment• Usually young and thin• No family history of diabetes• Common causes of death:

– Ketoacidosis– Hypoglycemia– Kidney failure– Heart attack

Type 2 DiabetesResistance to Insulin Action

• Gradual onset and progression over years• Strong family history• Usually overweight or obese• Diagnosis in middle age (this is changing

rapidly)• Many treatment options• Long survival even without treatment• Common causes of death:

– Heart attack– Kidney failure

• Blood sugar <50 mg/dL associated with brain dysfunction and can lead to death

• Type 1 diabetics more susceptible • Medication overdose: insulin or sulfonylureas• Taking medication but not eating, or unable to

eat• Taking medication and exercising strenuously• Symptoms

– Autonomic response: shaky, sweating, hunger, agitation

– Neuroglycopenic symptoms: confusion, lethargy, coma

• Treatment: oral glucose, glucagon, iv glucose

Hypoglycemia

• Occurs in type1 diabetics with frequent episodes of mild-moderate hypoglycemia

• Blunted autonomic reflex responses to hypoglycemia

• Only neuroglycopenic symptoms occur• Inability to think clearly (judgment is the first to

go) leads to inappropriate, ineffective or no response

• Greatly increased risk of death• Absolute avoidance of hypoglycemia for several

months restores responsiveness

Hypoglycemia Unawareness

Long Term Complications of Diabetes Microvascular

• Damage to the small arterioles becomes manifest in specific organs

• Retinopathy: leading cause of blindness in US• Neuropathy:

– loss of protective sensation in the feet and legs– Autonomic neuropathy: loss of cardiovascular and

gastrointestinal autoregulation

• Nephropathy: loss of functional nephron mass leading to kidney failure. Leading cause for ESRD and dialysis in the US

• Microvascular complications are slowed or prevented by tight glucose control (Hb A1c < 6.5%)

• Accelerated atherosclerosis of the major arteries• Myocardial infarction: heart attack risk is the same as

someone who has had an MI• Stroke: strong cofactor with hypertension• Peripheral vascular disease: strong cofactors are

smoking and male gender• Tight glucose control (Hb A1c < 6.5%) does not have an

advantage over good control (Hb A1c 7.5%)• Prevention strategy is to manage all risk factors:

smoking, blood pressure (< 130/80), LDL-C (<70 mg/dL), exercise, weight loss

Long Term Complications of Diabetes Macrovascular

Other Complications of Diabetes

• Increase with blood sugars > 200 mg/dL• Mucocutaneous fungal infections:

– Oral candidiasis– Vulvovaginal candidiasis

• Periodontal disease• Poor wound healing• Wound infections• Urinary tract infections• Skin and soft tissue infections

MANAGEMENT:Goals, Objectives &Tools

• Goals: – the long term outcomes desired by the patient

and the physician

• Objectives: – the objective easily measurable way points

marking progress towards the goals

• Tools:– techniques, medications and other

interventions used to achieve the objectives

Long-term Goals

1. Life Goals– Family– Employment– Avocations

2. Medical Goals-Prevent microvascular disease

-Decrease risk for macrovascular disease

-Prevent hypoglycemic complications

-Prevent the 5 D’s: death, disability, depression, dependency, destitution

Long-term Objectives

• Meaningful clinically

• Meaningful to the patient

• Objective

• Measurable

• Easily assessed by the patient

• Transparent: easily interpreted

Long-term Objectives

1. Normal function

2. No severe hypoglycemia

3. Hemoglobin A1c ≤ 7%

4. Maximum glucose <180 mg/dL checked 1 ½ to 2 hours after meals

Long-term Objectives

1. Normal function

2. No severe hypoglycemia

3. Hemoglobin A1c ≤ 7%

4. Maximum glucose <180 mg/dL checked 1 ½ to 2 hours after meals

Prioritized

Tools

1. Education

2. Diet

3. Glucose monitoring

4. Exercise

5. Medications

6. Devices

7. Doctors: exams, other labs

Tools

1. Education

2. Diet

3. Glucose monitoring

4. Exercise

5. Medications

6. Devices

7. Doctors: exams, other labs

Priority

Non Blood Sugar ObjectivesGaede P, et al. Effect of a multifactorial intervention on mortality in type 2 diabetes. N

Engl J Med 2008;358:580-91

1. BP < 130/80, lower is better: whatever it takes2. Lipid control, TC, LDL-C, TG: statin3. Diet:

-total calories-low carbohydrate diet

4. Obesity-diet, drugs, surgery-progressive weight loss, weight target

5. Exercise: rehab, PT, 10,000 steps daily6. Preventive Care: foot exam, immunizations, etc7. Manage albuminuria & CKD: ACE-I, BP control8. Mood, depression impairs management: ? SSRI

Modern Insulin Management:All Type 1 and some Type 2 patients

• Optimal insulins are synthetic & humanized• Basal insulin: very long acting

– Given daily, often in the evening– Humanized long acting: glargine (Lantus®), detemir

• Prandial insulin: very short acting insulins– Given with meals– Humanized very short acting: lispro (Humalog®), aspart,

glulisine

• Correction dose insulin– Lower glucose elevated above premeal target level– Given 30-60 minutes before meals– Humanized very short acting insulins

Other Drugs for Type 1 and Type 2

• Glucagon: – antagonizes insulin effect for rapid reversal of

hypoglycemia

• Older Insulins: suboptimal treatment choices, but less expensive– Animal derived intermediate acting: NPH,

Lente– Animal derived short acting: Regular– Fixed dose mixtures: 70/30 (70% NPH, 30%

Regular)

Drugs To Treat Type 2 Diabetes

• Injectable:– Insulin– Incretin (GLP-1) agonists

• Oral– Metformin– Sulfoylureas– TZDs: thiazolidinediones– DPP4 inhibitors– Gut absorption blockers– Meglitinides

Metformin

• Drug of first choice for type 2 diabetes• Generic and low cost• Twice daily dosing• Increases insulin effect• Decrease liver glucose production• Increases peripheral glucose uptake• Does not cause hypoglycemia• Does not cause weight gain• Side effects:

– Diarrhea– Lactic acidosis, rare

Sulfonylureas

• Older agents

• Inexpensive

• Long acting

• Stimulate insulin release by beta cells

• Side effects– Weight gain– hypoglycemia

Meglitinides

• Repaglinide, neglitinide

• Increase insulin release by a different mechanism than sulfonylureas

• Fast and short acting

• Taken before meals to lower post prandial glucose rise

• Side effects– hypoglycemia

Incretin (GLP-1) mimetics

• Two available: exenatide (Byetta®)• Injectable• Once daily• Expensive• Used alone rarely causes hypoglycemia• Does not cause weight gain• Side effects

– Nausea is very common (> 40%)– Slowed gastric emptying

DPP4 Inhibitors

• Oral once or twice a day

• Two drugs available: sitagliptin, saxagliptin

• Newer, expensive, second line

• Inhibit breakdown of incretins

• Do not cause weight gain

• Do not cause hypoglycemia

• Side effects: few

Thiazolidinediones

• Oral, intermediate duration, once or twice a day• Increase sensitivity to insulin action• Two drugs in class: pioglitazone (Actos®),

rosiglitasone (Avandia®)• Do not cause hypoglycemia• Cause weight gain• Side effects

– Fluid retention and heart failure– Possible increased risk of MI

Second Line Drugs

• Alphaglucosidase inhibitors (acarbose and others)– Blocks carbohydrate digestion– Slows glucose absorption– Used in combination with metformin– Flatulence and diarrhea

• Lipase inhibitors: orlistat (Xenical®)– Block fat digestion– Diarrhea

Hypoglycemia:Which patient should concern you?

• Type 1 on insulin

• Not obese

• History of hypoglycemia (high risk for hypoglycemia unawareness)

• Acute oral issues impairing chewing or swallowing

• Sedation

• Longer procedures

What signs should concern you?

• Anxiety

• Sweating

• Uncooperativeness

• Confusion

• Sedation

• Decreased pain response

What Should You Do?

• Immediately stop the procedure• If aware and cooperative, give something

to eat• If possible have the patient check their

glucose• For unresponsive patient:

– Call 911– Give glucagon if available– 50% dextrose intravenously– Do not put food in the mouth

Learning Objectives

• Appreciate the challenge of diabetes from the patient’s perspective

• Differentiate type 1 from type 2• Understand insulin action• Understand complications of diabetes• Recognize major classes of medications• Recognize side effects of each class• Recognize potential complications affecting

dental care

Diabetes Essentials 2011

Richard LeBlond, MD, MACPChief Quality Officer

Professor, Internal MedicineUniversity of Iowa Health Care

QUESTIONS?

Complications of Diabetes: Ketoacidosis

• Insufficient insulin• Glucose cannot enter muscle so glucose levels

rise• Absent insulin signal to liver and fat• Fat releases triglycerides which are metabolized

in muscle to ketoacids• Liver starts making glucose further increasing

glucose• Osmotic diuresis leads to volume depletion• Ketoacids produces metabolic acidosis

aggravated by volume depletion• Death from severe acidosis and hypotension

Treatment of Ketoacidosis

1. Replace volume deficits with normal saline, usually several liters

2. Intravenous insulin drip

3. Replace electrolytes, particularly KCl

4. Continue insulin drip even when glucose becomes normal

5. Transition to subcutaneous insulin after all metabolic abnormalities are corrected

Care at Home Locus of Care

Personal Organism Social Person

Shared Responsibility: Who is responsible and accountable for what

• Ask the patient “whose problem is this?”

– Repeat and wait until the patient (not the spouse, family member, etc.) acknowledges their responsibility

– The outcome is most dependent upon the patient’s not the doctor’s activities

– The patient will receive the benefits or consequences of the decisions and actions

What should we conclude?

• Benefit is achieved in reducing A1c from > 9.0 to <7.0%

• No clear benefit with lowering A1c to ≤ 6.5%• A1c is a continuous not dichotomous variable

– One studies “intensive” is the next study’s control• Recent studies show increased harm, including

death, with more intensive therapy • Severe hypoglycemia increased with intensive

therapy• Achieving tight control is resource intensive

(time, drugs, supplies, emotional)

In the absence of clearly-defined goals we become strangely loyal to performing daily trivia until ultimately we become enslaved by it.

-Robert Heinlein

Symptoms of Diabetes

• Weight Loss

• Increased Appetite

• Increased Urination– Large urine volumes– Frequent voiding at night

• Visual Changes: blurring

• Fatigue, decreased energy

Diabetes Management

• The patient not the doctor manages diabetes• Doctor, docere L. teacher• Diet: count carbohydrates and total calories• Exercise: regular aerobic exercise 30+ minutes >

3 days per week• Home glucose monitoring: a learning tool• Glucose lowering medications• Manage other risk factors: BP, cholesterol,

tobacco use

The main problem with communication is the assumption that it has occurred.

-George Bernard Shaw