DIABETES MELLITUS
Sepehr Khashaei, MD
Overview
• Prevalence increasing each year in US mainly due to
increase in obesity.
• 4,000 cases diagnosed daily.
• 7% of US population.
• Highest incidence in American Indians
• high incidence in Hispanics, Mexican Americans, and
African Americans.
• Caucasians have the lowest rate in the world.
• If you were born in 2000, your risk of developing any
kind of DM is 33% (males) and 39% (females).
• Twice the death rate of non-diabetics from CAD.
Overview (continued)
• 200 amputations daily.
• Life span is reduced by 12 years (males) and
19 years (females).
• Treatment accounts for at least 14% of US
health care expenditure.
Type 1 DM
•
•
•
•
Insuficent amount of insulin.
Immune-mediated
10% of patients with DM
Avoid using the terms IDDM or juvenile-onset
diabetes DM.
• Sporadic (usually not hereditary).
• Treated with insulin
Type 1 DM (continued)
• Patients prone to ketosis.
• Associated with autoimmune diseases
especially: hypo/hyperthyroidism, adrenal
insuficiency, celiac sprue, vitiligo, B12
deficiency, maysthenia gravis.
Type 1 DM treatment
• Use long-acting insulin such as NPH, glargine
and detemir to cover the fasting and pre-meal
states
AND
• Use short-acting insulin such as regular, lispro
and aspart to cover meals.
Type 1 DM treatment (continued)
• Can also be treated with a continuous,
subcutaneous insulin infusion done with a
small pump that provides a continuous basal
rate all day, with programmed increases prior
to meals.
• Pumps carry a danger of hypoglycemia, and
this may be fatal if it occurs at night or is
otherwise unrecognized especially in someone
with CAD.
COMMONLY USED INSULINS IN THE U.S.
GENERIC
RAPID ACTING
Lispro
Aspart
Regular
INTERMEDIATE
NPH
LONG ACTING
Glargine,Detemir
BRAND
FORM
Humalog
Novalog
Analog
Analog
Humulin R or Novolin R Human
Humulin N or Novolin N Human
Lantus,Levemir
Analog
GENERIC
BRAND
FORM
MIXTURES
70% NPH/
30% regular
75% NPH/
25% lispro
Humulin 70/30 Human
or Novolin 70/30
70% NPH/30%
aspart
Novolog
70/30
Humalog Mix Analog
75/25Novolog
Analog
TIME OF ACTION OF INSULINS
ONSET
PEAK (hr)
DURATION(hr)
Lispro,
aspart
Regular
< 15 min
0.5-1.5
3-4
0.5-1 hr
2-3
3-6
NPH
2-4 hr
6-10
10-16
Glargine,
detemir
Ultralente
2-4 hr
Peakless
(not)
10-16
18-24
6-10 hr
18-20
Insulin Pump
Dawn effect
• Increased blood glucose between 4 and 7 am
• No preceding hypoglycemia
• The cause is transient, mild, insulin resistance
due to the normal, early-morning rise in
cortisol and GH.
Somogyi effect
• Hyperglycemia after immediate preceding
hypoglycemia that theoretically stimulates the
adrenal gland to release cortisol and
temporarily increase blood glucose levels.
• Occurs any time of the day but calssically at
night (with associated headaches and
nightmare).
How to differentiate between Dawn
phemomenon and Somogyi effect?
• Check a 2am blood glucose:
– If low = somogyi effect
• Treat Somogyi effect by decreasing evening
insulin.
Type 2 DM
•
•
•
•
•
90% of DM
Mechanism is insulin resistance
Strongly related to obesity (80% are obese).
Strongly hereditary
Avoid using the terms NIDDM or adult-onset
DM.
• Usually treated initially with oral hypoglycemic
agents.
• The age of onset has been decreasing.
DM type 2 (continued)
• More likely to get hyperosmolar nonketotic
state than DKA.
Type 2 DM treatment
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Diet and exercise and weight loss
Insulin
Oral hypoglycemic medication.
Injectable hypoglycemic medications
Insulin +/- hypoglycemic medication
Hypoglycemic medications
– Sulfanylureas
– Glinides
– Biguanides
– Thizaolidinediones (TZD)
– α- Glucosidase Inhibitors (AGI)
– Amylin Analogs
– Incretin Mimetics
– Dipeptidyl-Peptidase 4 Inhibitors (DPP4I)
Sulfanylureas
• Increase insulin secretion from the pancreas.
• 1st generation (acetohexamide,
chlorpropamide, tolazamide and tolbutamide
• 2nd generation (glipizide, glyburide and
glimepiride)
• 2nd generation drugs preferred over first
generation and less expensive.
• Approved for use in combination with most
other drugs except glinides.
Sulfanylureas (continued)
• Half-life is long
• Fast acting (can titrate to maximal dose in 2-4 weeks).
• Hypoglycemia can persist in states of overdose or
renal impairment.
• Use with caution in elderly and in declining renal
function.
• Severe hypoglycemia mandates an admission to the
hospital because of need for frequent monitoring and
possible need for iv glucose therapy.
Glinides
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•
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Repaglinide and nateglinide
Increase insulin secretion from the pancreas
Rapid-acting
Short half-life
Major effect is on postpranial glucose.
Biguanides
• Metformin
• Reduce hepatic glucose production and lowers
insulin resistance.
• Used as the first line of treatment (even in
prediabetes) if no contraindications
• Decreased mortality.
• No weight gain (and possibly some weight loss)
• No hypoglycemia when used alone
• Decreases LDL and triglycerides.
• Decrease risk of CAD (cardioprotective)
Biguanides (continued)
• Side effect: dose-related abdominal pain and
diarrhea and propensity for causing lactic
acidosis
• Contraindicated if creatinine ≥ 1.5 in a male or
≥ 1.4 in a female, decompensated or
significant CHF, and acute or chronic metabolic
acidosis, and hepatic insuficiency.
• Hold in acutely ill patients and in those
scheduled for contrast procedures or surgery
Thiazolidinediones (TZD)
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Rosiglitazone and pioglitazone (preferred)
Enhance insulin sensitivity
Very effective for reducing insulin resistance.
Take 6 wks to 3 months to take effect.
Extremely effective in treating NASH and POD
Modest reduction in blood pressure
Increase HDL and decrease triglycerides
Adverse effects: edema and weight gain.
– Contraindicated in patients with class III or IV CHF
and CAD
• Monitor the LFT’s periodically.
Amylin Analogue (pramlintide)
• Amylin is a hormone secreted by pancreatic
beta cells along with insulin and helps to
regulate influx by suppressing glucagon and
slowing stomach emptying.
• Centrally mediates modulation of appetite
decreasing food intake
• Used with insulin to lower post prandial blood
sugars
• Also used in Type 1 DM
• Given as SC injection
Incretin Mimetics (exenatide)
• Enhance glucose dependent insulin secretion in
response to food
• Has glucagon-like peptide-1 (GLP-1) activity
• Suppresses glucagon
• Delayed gastric emptying
• Acts in brain to affect satiety (therefore helps with
losing weight)
• GLP-1
– Secreted from L cells in intestine
– Most well characterized incretin
– Decreased in Type 2 diabetes
Exenatide (continued)
• Decreases plasma glucose acutely to near normal levels
• Long duration in plasma after SC injection
• Approved for use in patients with BG uncontrolled with metformin or
sulfonylureas.
• Hypoglycemia not seen if used alone or with metformin.
• > 85% lose weight.
• Can lower lipids and blood pressure.
• Requires injection in AM and PM.
• Is expensive
• Improves postpranial and fasting glucose.
• D/c if pancreatitis. Don’t start if h/o pancreatitis.
• Can cause renal failure. Do not use if GFR <30 or at high risk of acute
renal failure.
• Major SE: nausea (tends to decrease with time). Start with lower
dose if nausea.
• Reduce dose of sulfanylurea by 50% when adding this. Give for one
month and if glucose still high, increase sulfanylurea by 25%.
α- Glucosidase Inhibitors (AGI)
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•
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Acarbose and miglitol
Delay carbohydrate absorption in the gut.
Biggest effect is on postpranial glucose.
Given three times a day with meals.
GI side effects (flatulence, abdominal bloating,
and diarrhea) makes them intolerable to a lot
of patients.
Dipeptidyl-peptidase 4 inhibitors
• Sitagliptin
• Slow the inactivation of natural incretins, such
as glucagon-like peptide 1 (thereby increasing
their concentration).
• Biggest effect is on postpranial glucose.
• Associated with weight loss.
• Lower instances of hypoglycemia.
• Early institution of treatment of DM
at a time when the A1C is not
significantly elevated is associate
with improved glycemic control over
time and decreased long term
complications.
• Long-acting insulin: Starting dose is
typically at a 0.2 units per Kg per day,
and titrated in increments of 2 units
approximately every 3 days. Can
titrate faster in hospitalized patients.
• Combination of oral agent with
insulin is no better than adequate
insulin alone.
• Consider starting the patient on insulin
when HgbA1C >9.0
• Do not measure or treat lipids in a
diabetic patient till BG is under control.
• Get Fasting blood glucose down first and
then work on postpranial BG control.
Other causes of DM
• Pregnancy (Gestational)
• Medication-Induced
E.g. niacin, steroids, thiazides, oral
contraceptives, beta-blockers.
• Endocrinopathies (Cushing’s,
acromegally)
• Pancreatic defects and injury.
Impaired Fasting Glucose
• Avoid using the term pre-diabetes
• Diagnosed by:
1. Fasting plasma glucose 100-125 on
two different occasions or
2. 2-hr plasma glucose of 140-199 after a
75-gm glucose load) on two different
occasions or
3. One of number 1 & one of number 2.
Diagnosis of DM
1. Fasting (at least 8 hours) blood glucose ≥ 126
on two different occasions or
2. Random plasma glucose ≥ 200 on two
different occasions with symptoms (polyuria,
polydipsia, weight loss, fatigue), or
3. 2-hr plasma glucose ≥ 200 after a 75-gm
glucose load (done after an 8 hour fast), or
4. Hemoglobin A1C ≥ 6.5 on two separate
occasions.
5. Any combination of two of the 1-4.
Screening for DM
• Screen the following patients for DM annually
beginning at age 30 (FPG preferred):
– 1st degree relatives with DM
– CAD
– Acanthosis nigricans and BMI ≥ 25
– Sedentary
– Non-caucasion race
– h/o impaired fasting glucose
– HTN
Acanthosis Nigricans
Acanthosis Nigricans
Acanthosis Nigricans
Acanthosis Nigricans
• Acanthosis nigricans is common in younger
patients and correlates with insulin resistance.
In older patients, it suggests GI malignancy.
Screening (continued)
– Hyperlipidemia
– H/o gestational diabetes
– h/o delivery of > 9 lb infant
– Polycystic ovarian disease
– Pscyhiatric disease
• Without the risk factors mentioned, start
screening at age 45 years.
Screening (continued)
• Important point: Finger sticks are acceptable
for self monitoring on known DM, but only
plasma/serum should be used for diagnosis.
This is because whole blood (finger stick)
glucose values are about 15% less than
serum/plasma values.
Impaired fasting glucose
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•
•
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1/3 will develop Type 2 DM
1/3 will normalize
1/3 will stay as impaired fasting glucose
Still have risk for developing microvascular
disease.
• Promote weight loss , regular exercise and low
sodium, high-fiber, low fat diet.
Impaired fasting glucose
(continued)
• Consider metformin or acarbose in high-risk
patients.
• Lipid, blood pressure goals, and aspirin
therapy should be the same as for diabetes.
• Annual urine test for microalbuminuria and
and annual fasting lipids.
• Twice yearly Hgb A1C.
Hgb A1C
• Check again in 6 months if no change in DM
medications
• Check again in 3 months if any change in DM
medications
• Goal is to keep Hgb A1C < 7 (great control)
• 7-8 is considered fair control
• 8-9 is considered moderate control
• >9 is considered poor control
Long-Term Complications of IDDM
• Visual impairment
• Blindness
• Renal failure
• Stroke
• Amputation
• MI
• Median survival after
diagnosis of IDDM (yr)
14%
16%
22%
10%
12%
21%
36
Other Therapies
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ASA
ACEI
BP control
Lipid control
Immunizations
Rx for neuropathic pain
Rx for gastroparesis
Rx for ED
Diabetic Foot Exam
Diabetic Foot Exam
Diabetic Foot Exam
Diabetic Foot Exam
Diabetic Foot Exam
(Monofilament)
Diabetic Foot Exam (bedside
doppler)
Diabetic Foot Chart
Diabetic Foot Ulcer
Patient advice for foot care
• Avoid going barefoot, even in the home.
• Test water temperature before stepping into a bath.
• Trim toe nails to shape of the toe; remove sharp
edges with a nail file. Do not cut cuticles.
• Wash and check feet daily.
• Shoes should be snug but not tight and
customized if feet are misshapen or have ulcers.
• Socks should fit and be changed daily.
Hypoglycemia
• Daytime episodes
– are recognized by autonomic symptoms
(sweating, nervousness, tremor and hunger)
• During sleep
– may produce no symptoms or cause night sweats,
unpleasant dreams, and early-morning headache
• If hypoglycemia is not aborted by the
countercurrent regulatory mechanisms or by
ingestion of carbohydrate, CNS symptoms
develop (confusion; abnormal behavior, loss of
consciousness or convulsions)
• Hypoglycemia unawareness:
– as diabetes progresses, particularly with the
development of neuropathy, epinephrine-induced
symptoms may become blunted and lose their
effectiveness as warning signals
Glucagon
DKA (diagnosis)
• Blood glucose >250 and
• Arterial PH of 7.3 or less and
• Moderate or severe ketonemia
Precipitating factors
• Infection (most common pneumonia and
UTI)
• Noncompliance with insulin therapy
• ETOH or drug abuse
• Silent MI
• Stroke
• Pancreatitis
• Trauma
• Drugs (corticosteroids, higher dose of
thiazide diuretics)
DKA (Laboratory findings)
• Significantly elevated plasma
glucose
• Wide anion gap metabolic
• Plasma sodium – tends to be low
in the face of modest osmolar
concentration because of the
hyperglycemia that draws
intracellular water into the plasma
space
 Plasma potassium – initial normal to
high (due to the translocation of K
out of the cells into the extracellular
fluid).
Plasma phosphate – typically in
negative phosphate balance due to
decreased phosphate intake and
phosphaturia caused by the
glycosuria-induced osmotic diuresis
Treatment of DKA
• Determine hydration status: start IVF
0.9% normal saline
• No insulin until potassium level back
• Insulin: +/- start with loading dose of
15-20U Reg insulin, then 0.1 U/kg/hr
as iv infusion (if serum glucose level
doesn’t fall by 50-70 mg/dL in the first
hour, double insulin infusion)

When serum glucose < 250 mg/dl
change to 5% dextrose in 0.45 % saline at 100200 mL/h with adequate insulin coverage
(0.05 to 0.1 U/kg/h as iv infusion or 10U sc q
2h). Keep glucose at 150-200 until metabolic
control is achieved

Potassium: if K < 3.3
hold insulin and give 40 mEq/h of KCL;
when K > 5.5, don’t give KCL; when K is
between 3.3 and 5.5, give 20 to 30
mEq of
potassium in each liter of IVF
FAMOUS BELCH
• F=Feet
• A=Aspirin
• M=microalbumin
• O=ophthalmological exam
• U=u/a
• S=smoking
• B=Blood pressure
• E=Education
• L=Lipids
• C=Creatinine
• H=HgbA1C
The letters in Bold should be done biannually and the
rest annually.