Type II Diabetes

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Type II Diabetes

• Matthew Love, M.D.

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Case 1

• Fred Banting, a 52 year-old man, complains of
  polyuria and polydypsia for three weeks. On
  questioning, he also admits to dizziness on
  standing.
• On exam, his BP is 135/80, Pulse 95. He is 58
  tall, weighs 220 and has acanthosis nigricans.
• Urine dipstick is for glucose. Fingerstick
  glucose is 188. Point of Care Hemoglobin A1c is
  8.3.
• Does this patient have Diabetes?

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Diagnosis
Method Threshold Value Advantages Disadvantages
Fasting Plasma Glucose gt 126 mg/dl Time since last meal easy to define ADA preferred Cheap Inconvenient Unstable
Random glucose gt200 symptoms Convenient Less reproducible
HbA1c 6.5 Correlates with disease process Stable Cost
OGGT gt200 _at_ 2 hours Pregnancy Cumbersome
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Prediabetes

• Impaired fasting glucose 100 lt FPG lt 126
• Impaired glucose tolerance OGTT result at 2h
  between 140-199.
• Hemoglobin A1c of 6.0 6.4

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Remember the Pathogenesis
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Remember the Pathophysiology
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Case 2

• Dulce Diente is a 37 year-old female with a
  family history of diabetes. She wants to be
  checked for diabetes because she has gained a lot
  of weight, she keeps getting yeast infections and
  her urine tastes sweet.
• Physical exam is normal except for a BMI of 29.
• FPG checked by fingerstick on her fathers
  glucometer has been 110-120. Point of Care HbA1c
  comes back at 6.8
• Should she be started on medicine? Is there
  anything that can be done to prevent the
  progression of her diabetes?

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Diabetes Prevention ProgramResults
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Diabetes Prevention ProgramChange in weight
Physical Activity
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PREVENTION TRIALS
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Case 3

• Isabel Fadiman is a 41 year-old African-American
  female who presents for a check-up. She has no
  complaints. Past medical history includes
  gestational diabetes during her last pregnancy
  five years ago. Family history is positive for
  two brothers and both parents with Type 2 DM.
  She does not smoke.
• On exam, her BP is 120/80 and her BMI is 27.
  There is no acanthosis nigracans or any other
  abnormality.
• Should she be screened for diabetes?

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Diabetes Screening Recommendations
Organization Recommendation
US Preventive Services Task Force The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for type 2 diabetes in asymptomatic adults with blood pressure of 135/80 mm Hg or lower. The USPSTF recommends screening for type 2 diabetes in asymptomatic adults with sustained blood pressure (either treated or untreated) greater than 135/80 mm Hg.
American Diabetes Association For adults who do not have diabetes risk factors, consider screening every 3 y starting at age 45 y, particularly if body mass index gt25 kg/m2 Screen adults lt 45 y of age if they are overweight and have another diabetes risk Factor
Canadian Diabetes Association Evaluate all patients for type 2 diabetes risk annually Screen patients without diabetes risk factors every 3 y starting at age 40 y Consider earlier, more frequent screening for patients with diabetes risk factors

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Risk Factors for Type 2 Diabetes

• Age gt 45 y
• First-degree relative with type 2 Diabetes
• African-American, Hispanic, Asian, Pacific
  Islander, or Native American ethnicity
• History of gestational diabetes or delivery of
  infant weighing 9 lbs
• Polycystic ovary syndrome
• Overweight, especially abdominal obesity
• Cardiovascular disease,hypertension,
  dyslipidemia, or other
• metabolic syndrome features

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Initial Evaluation

• Symptoms
• Exam BP, BMI, Feet
• Labs
• HbA1c
• Ualb/cr
• Chemistry (Cr, LFTs)
• EKG
• Referrals
• Dietician
• Glucometer Teaching
• Ophthalmology
• Podiatry

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Blood Glucose Monitoring
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Glucometer Operation
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Case 4

• Matt Forman is a 54 year-old man with newly
  diagnosed Type II Diabetes. His FPG is 148 and
  his HbA1c is 7.8 . Physical is normal except
  for BMI of 28. Except for the glucose values,
  his laboratory exams are normal.
• How should he be treated?

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Treatment non-pharmacologic Diet

• Carbohydrates
• Should comprise 45-65 of total calories
• No concentrated sweets (soda, juice, desserts)
• No white starches (especially rice and pasta)
• Fresh vegetables and fruits rather than canned
• Fats
• Should comprise lt 30 of total calories
• Saturated fats should be lt 7

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Treatment non-pharmacologic Exercise
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Treatment pharmacologic Oral Agents
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Metformin

• No weight gain
• No hypoglycemia
• Cheap, generic, old
• GI side effects frequent
• Rare but serious lactic acidosis
• Start at 500 bid with meals
• Titrate up quickly to 1000 bid or 850 tid

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Sulfonylurea

• Cheap, generic, old
• Equally effective
• May cause hypoglycemia
• Weight gain
• Start at low dose, increase gradually

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Thiazolidinediones TZD

• Increase glucose uptake and decrease glucose
  production
• Equally effective
• May preserve beta-cell function
• Newer, more expensive
• Fluid retention
• May cause xs MIs

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Incretin mimetics
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Incretin-based therapies
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Alpha-glucosidase Inhibitors

• Lower postprandial glucose and A1c
• Less potent
• No weight gain
• Cause flatulence
• Contraindicated in cirrhosis
• Take with first bite of meal

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Case 4

• Matt Forman is a 54 year-old man with newly
  diagnosed Type II Diabetes. His FPG is 148 and
  his HbA1c is 7.8 . Physical is normal except
  for BMI of 28. Except for the glucose values,
  his laboratory exams are normal.
• After 6 months of a diabetic diet and increased
  exercise, his HbA1c is 8.1
• How should he be treated?

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Case 4

• Matt Forman is a 54 year-old man with newly
  diagnosed Type II Diabetes. His FPG is 148 and
  his HbA1c is 7.8 . Physical is normal except
  for BMI of 28. Except for the glucose values,
  his laboratory exams are normal.
• After 6 months of a diabetic diet and increased
  exercise, his HbA1c is 8.1
• After 6 months of Metformin at a dose of 1000 mg
  bid, his HbA1c is 7.1
• How should he be treated?
• What is the glycemic control target?

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Glycemic Control Target Good Control Reduces
Microvascular Complications
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Glycemic Control Target The UKDPS the largest
and longest study in Type II DM

• Microvascular complications were reduced 25 in
  the intensive- therapy group
• Epidemiologic analysis showed that for every 1
  reduction of HbA1c
• 35 reduction in microvascular complications
• 25 reduction in diabetes related deaths
• 7 reduction in all cause mortality
• 18 reduction in myocardial infarction
• No lower threshold

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Glycemic Control Target Macrovascular
Complications

• ACCORD trial Action to Control Cardiovascular
  Risk in Diabetes

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Glycemic Control Target

• Current Recommendations from the ADA
• The Benefits of Intensive Glycemic Control on
  Macrovascular Complications vary based on the
  population being treated
• Those most likely to benefit from intensive
  control are those with shorter duration of DM, no
  known vascular disease, and without severe
  hypoglycemia
• The risk of intensive glycemic control may
  outweigh the benefits in those with a long
  duration of DM, known vascular disease, or
  symptomatic severe hypoglycemia

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Case 4

• Matt Forman is a 54 year-old man with newly
  diagnosed Type II Diabetes. His FPG is 148 and
  his HbA1c is 7.8 . Physical is normal except
  for BMI of 28. Except for the glucose values,
  his laboratory exams are normal.
• After 6 months of a diabetic diet and increased
  exercise, his HbA1c is 8.1
• After 6 months of Metformin at a dose of 1000 mg
  bid, his HbA1c is 7.1
• How should he be treated?
• A second agent should be added

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Case 4 Algorithm
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Case 5

• Norman P. Hagedorn is a 64 year-old man with Type
  II Diabetes for 12 years. He also has CAD, s/p MI
  and CABG, HTN, gout, and BPH. Medications
  include metformin, glyburide, pioglitazone, and
  sitagliptin at maximal doses. Previously, his
  HbA1c were always in the 7.0-7.9 range, however
  his last two HbA1cs, three months apart, are 9.8
  and 10.9. Previous attempts to introduce insulin
  injections have met with adamant refusals.
• What might have happened to his glycemic control?

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Case 5

• Norman P. Hagedorn is a 64 year-old man with Type
  II Diabetes for 12 years. He also has CAD, s/p MI
  and CABG, HTN, gout, and BPH. Medications
  include metformin, glyburide, pioglitazone, and
  sitagliptin at maximal doses. Previously, his
  HbA1c were always in the 7.0-7.9 range, however
  his last two HbA1cs, three months apart, are 9.8
  and 10.9.
• Bedtime NPH 10 Units is added to his metformin.
  Glyburide , pioglitazone, and sitagliptin are
  discontinued. After following the titration
  schedule for six weeks, he is on 25 units NPH and
  morning fingersticks are 95-125.

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Case 5

• Norman P. Hagedorn is a 64 year-old man with Type
  II Diabetes for 12 years. He also has CAD, s/p MI
  and CABG, HTN, gout, and BPH. Medications
  include metformin, glyburide, pioglitazone, and
  sitagliptin at maximal doses. Previously, his
  HbA1c were always in the 7.0-7.9 range, however
  his last two HbA1cs, three months apart, are 9.8
  and 10.9.
• Bedtime NPH 10 Units is added to his metformin.
  Glyburide , pioglitazone, and sitagliptin are
  discontinued. After following the titration
  schedule for six weeks, he is on 25 units NPH and
  morning fingersticks are 95-125.
• After 3 months with continued good am
  fingersticks, HbA1c is 8.5. What would you do
  now?
• Pre-dinner fsg are 160-180, so NPH is switched to
  glargine and eventually titrated up to a dose of
  35 U daily.
• Now am fsg are 80-110 and pre-dinner are 95-120.
• 3 months later HbA1c is 8.0. What would you do
  now?

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Diabetes Treatment Algorithm
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Diabetes and Hypertension - UKDPS

• For each 10 mm decrease in SBP
• Microvascular complications ? 13
• Death ? 15
• MI ? 11

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Diabetes Lipids - Heart Protection Study

• Primary prevention with risk factors
  (hypertension, diabetes, and CVA)
• 2x2 factorial design simvastatin 40
  mg/day, antioxidant cocktail (600 mg vitamin E,
  250 mg vitamin C, 20 mg beta carotene)
• N 20,000 subgroups include
  Women (n 5,000) Elderly (gt65, n
  10,000) Diabetics (n 6,000)
  Stroke (n 3,000)
  Hypertension (n 8,000)
  Noncoronary vascular disease (n 7,000)
  Low to average blood cholesterol (n 8,000)

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Heart Protection Study Vascular Events by
Baseline Disease
Risk ratio and 95 CI
Baseline feature Simvastatin (n10,269) Placebo (n10,267)
Previous MI 1007 1255
Other CHD (not MI) 914 1234
No prior CHD
CVD 182 215
PVD 332 427
Diabetes 279 369
All patients 2042 (19.9) 2606 (25.4)
Statin better
Statin worse
? 24 2.6 (2P lt0.00001)
0.4
0.6
0.8
1.0
1.2
1.4
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Diabetes/HTN Lipids Steno-2

• Intervention was intensive lowering of BP,
  lipids, and A1c
• Macrovascular complications reduced 50 in
  intensive treatment group over 13 years

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Diabetes HTN Lipids
Clinical Parameter Target
LDL cholesterol lt 100
Blood Pressure lt 130/80
HbA1c lt 7
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The Routine Followup Visit

• Glycemic Control
• Fingersticks
• Daily if previously at target and on orals or
  glargine
• More frequently if not at target or more
  complicated regimen
• Symptoms of hypoglycemia hyperglycemia
• Adherence to Diet, Exercise, Medication
• Ongoing Education
• Ongoing Screening for longterm microsvascular
  complications (at least yearly)
• Nephropathy (Ualb/cr), Neuropathy (monofilament)
  , retinopathy
• Control of other macrovascular risk factors
• LDL lt 100
• BP lt 130/80

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Question 1 What are the symptoms of diabetes?

• Hyperglycemia
• Tm of kidney for reabsorption of glucose gt 160,
  sugar pulls water, leading to polyuria the
  dehydration stimulates thirst
• Polyphagia and weight loss
• Blurry vision glucose deposits in cornea
• Yeast infections
• Volume Depletion
• - Orthostatic dizziness
• Nonspecific symptoms
• Headaches, weakness

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Question 2 the following patient is taking 25 U
of NPH in the morning and 16 Units at bedtime.
What adjustments would you make to her regimen?
Day 8 a.m. fasting 6pm pre-dinner 10 pm bedtime
S 140 120
M 174 100
T 144 220
W 155 184
Th 151 84
F 133 65 179
Sa 130 112
S 149 108
M 145 188
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Question 3 this patient is using 45 Units of
Lantus at bedtime and has the following
fingersticks
Day 8 a.m. fasting 6pm pre-dinner 10 pm bedtime
S 90 85
M 82 85
T 99 106
W 83
Th 82 84
F 96 112
Sa 100 88
S 120 123
M 100 88
HBA1c is 7.8 What could explain this? What
would you recommend?
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Question 4 this patient is taking 1000 mg of
Metformin bid and has the following fingersticks
Day 8 a.m. fasting 6pm pre-dinner 10 pm bedtime
S 90 88 125
M 82 99 123
T 99 101 165
W 82 87 101
Th 82 94 112
F 96 96 140
Sa 100 121 130
S 120 88 115
M 100 99 113
What would you expect the HbA1c to be?
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Translating the A1c into Estimated Average
Glucose Values