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1. 1 Diabetes Mellitus Frank Grimaldi Jr.
MSEd, MMS, PA-C, ATC, LAT
2. 2
3. 3 You’ve seen the headlines:
4. 4 The New York Times: “The diabetes epidemic will overwhelm health care resources everywhere if governments do not wake up and take action”
5. 5 USA Today: “73 million have diabetes or are at risk in U.S. There’s a tremendous problem … that really represents a genuine epidemic.”
6. 6 Time Magazine: In its cover story “Why Are So Many of Us Getting Diabetes?” Time called the disease “an epidemic that keeps on raging,” and said “What alarms public health experts the most is the speed at which diabetes has spread.”
7. 7 DIABETES: FAST FACTS 250 Million sufferers today, 350 million by 2025
Monitoring, pharmaceuticals and insulin: $50+ billion
In the US, 1 in 6 healthcare dollars is spent on diabetes and conditions caused by diabetes
Diabetes is now the number – four cause of death worldwide
8. 8 A Worldwide Epidemic Today: 250 Million Sufferers
2025: 350 Million
9. 9 Countries with the highest total number of sufferers: INDIA 35.5 Million
CHINA 23.8 Million
USA 16 Million
RUSSIA 9.7 Million
JAPAN 6.7 Million
10. 10 Company (Division)Diabetes Related US Sales Abbott Laboratories ……. $350 million
Bayer ……………………. $355 million
Johnson & Johnson (LifeScan) $825 million
Roche Holding …………. $500 million
11. 11 Diabetes Mellitus Affects 16 million Americans…more common in Black and Hispanic
Leading risk factor of CAD, CVA, blindness and kidney failure
Liver and pancreas responsible for the body’s fuel supply.
12. 12 Diabetes Mellitus Functional definition (from 30 years ago)
Disorder of carbohydrate management
Normal physiology:
Food digested, sugar converted to glucose, absorbed via portal system to liver. Converted to glycogen. Excess glucose goes to muscles, converted to glycogen.
13. 13 Diabetes Predisposing factors
Heredity
Obesity
Disease of pancreas
Pituitary tumors
Adrenal tumors, hyperplasia
Exhaustion of beta cells (usually preceded by hypoglycemia)
Induced by growth hormone, and cortisol
14. 14 Diabetes - types Type 1
Islets totally incapable of making insulin
Type 2
Islets can make insulin
15. 15 Diabetes - effects It is a total body disease
Vascular damage: walls of small arteries become thickened, occluding the lumen
Damage to kidneys, nerves, retina, feet
Abnormal fat metabolism
Ketosis, acidosis, coma
Gallstones
Elevated glucose enhances infections
16. 16 Pancreas Exocrine
acinar portion…digestive enzymes
endocrine
beta cells…insulin
moves glucose into tissues
alpha cells …glucagon
antagonizes insulin by releasing glycogen from liver
delta cells….somatostatin
inhibits release of glucagon and insulin
inhibits gastrointestinal motility
17. 17 Glucose metabolism 2/3 of glucose derived from food stored as glycogen in liver and muscle.
Liver supplies the whole body; muscle does not export. Muscles and adipose tissue prefer fatty acids for energy.
When stores are full, excess converted to fat
Liver can synthesize glucose from amino acids, glycerol and lactic acid “gluconeogenesis”
CNS must have glucose - lack can cause anything from confusion to coma to necrosis.
18. 18 Insulin Only hormone in the body that lowers sugar
Promotes glucose uptake by cells
Enables cells to metabolize glucose
Promotes storage of fat - inhibits breakdown
Promotes storage of glycogen
Inhibits gluconeogenesis
Increases protein synthesis.
Inhibits conversion of protein to glucose
19. 19 Catecholamines Epinephrine and norepinephrine
Decreases insulin
Decreases movement of glucose into cells
Increases glycogenolysis
Mobilizes fatty acids
20. 20 Growth hormone Antagonizes insulin (reverse is also true)
Increases protein synthesis (builds muscle)
Increases fat burning
Decreases cell use of glucose
Release is inhibited by insulin and glucose
Release is enhanced by fasting, heavy exercise, trauma and fever.
21. 21 Glucocorticoids Most powerful is cortisol
Stimulates gluconeogenesis
Slightly decreases tissue use of glucose
Production stimulated by:
hypoglycemia
infection
pain, trauma, surgery
strenuous exercise
anxiety
22. 22 Diabetes From Greek for “running through” and “sweet”
Definition: disorder of carbohydrate, protein and fat metabolism by relative deficiency of insulin.
Classification - (old definition changed in 1997)
Type I…insulin dependent
Type II…non-insulin dependent
23. 23 Diabetes - types Type 1 (note Arabic # instead of Roman)
20% of all diabetics
Due to destruction of beta cells
No insulin produced at all
1A is due to immune destruction of beta cells
1B is idiopathic
1A used to be called “juvenile diabetes”, and is usually seen in the young, but can affect any age. Very prone to ketoacidosis.
80% have islet cell antibodies
50% have insulin antibodies
24. 24 DM - type 2 80% of all diabetes
Seen in older, overweight individuals but incidence in adolescents increasing at alarming rate.
Truncal and intra-abdominal obesity
Defect may be:
impaired production of insulin
neutralization by antibodies
cellular resistance - eventual beta cell exhaustion
increased gluconeogenesis
25. 25 DM - type 2 Secondary diabetes
Pancreatic disease
mumps, rubella, coxsackie
chemical toxins, esp. nitrosamine
Don’t bring home the bacon
Severe chronic pancreatitis or surgical removal
Drugs: thiazides ( by lowering K), cortisol, levodopa, BCP, phenothiazines, dilantin
26. 26 Gestational diabetes Occurs during pregnancy
- be suspicious of large for age babies
Low risk:
- under age 25, normal weight, no family history of DM, Caucasian. Anyone else should be screened at 24 weeks.
If diet does not control, insulin must be used. Oral agents contraindicated.
27. 27 DM - clinical presentation Type 1:
usually sudden onset. 3 P’s and weight loss. (Polyuria-excessive urination, Polydipsia- excessive thirst, Polyphagia-excessive eating)
Type 2
slow onset, overweight, 2 P’s.
Also look for blurred vision, fatigue, paresthesias, skin infections, esp. toenails and yeast infections in women.
Defn: FBS > 126 or random > 200 with SSx.
28. 28 DM - diagnostics (ADA) fasting blood sugar > 126
normal is < 110
glucose tolerance test (75 g. - 100 if pregnant)
normal FBS
return to normal in 2-3 hours
Glycohemoglobin A1C
Gives 2-3 month average of blood sugar
normal is under 6% > 8% requires treatment
29. 29 Treatment Most important is diet. Need consistent food intake and exercise. Weight loss essential
Medications - oral
sulfonylureas - glyburide and glipizide (glucotrol, glynase, diabeta and amaryl). Stimulates beta cells to release more insulin.
Biguanides - metformin (glucophage). Decreases gluconeogenesis. Increases cell sensitivity to insulin
glucosidase inhibitors - acarbose. Delays absorption of glucose from intestine
30. 30 Treatment - insulin Destroyed in stomach, must be taken by injection.
Measured in units…
Most come in 100u / cc.
Four types:
regular…shortest acting
NPH…intermediate
Lente and Ultralente…long acting
Human insulin widely available…Eliminates old problem of antibodies to beef and pork. 70/30 good for unsophisticated patients. BID dosage
31. 31 Insulin types
32. 32 Complications - acute Onset within 24 hours
Diabetic ketoacidosis DKA
usually seen with Type 1
Liver cannot metabolize and kidneys cannot excrete
Hyperglycemia (>250)
Ketosis (positive urine dipstick)
Metabolic acidosis (HCO3 < 15; pH <7.3)
May mimic “flu” Polyuria, polydipsia, nausea, vomiting, abdominal pain, breath smells like booze.
33. 33 Complications - acute HHNK - Hyperglycemic, hyperosmolar, non-ketotic coma. Onset 2 days to 2 weeks.
Osmolarity > 310
Glucose > 600
Usually seen with Type 2
exhibiting increasing insulin resistance, esp. after gorging on CHO.
Presents with marked dehydration and CNS SSx often mimicking a stroke.
Must correct S-L-O-W-L-Y to prevent cerebral edema. Watch K+ levels.
34. 34 Complications - acute Hypoglycemia
Glucose < 50
Causes:
Not enough to eat (or forgot)
Too much insulin (or pills)
Did not allow for exercise
CNS- confusion, delirium, coma
Autonomic - hunger, anxiety, SWEATING, tachycardia.
If patient is conscious - give OJ. Otherwise injection of glucagon, glucose gel in mouth, or 50% glucose by IV push.
35. 35 Complications - long term Neuropathies - peripheral
Obstruction of vessels that supply nerves
Demyelination (destroy or remove the myeylin sheath of the nerves)
Sensory
Paresthesias
Decreased sensitivity to pain, temperature and light touch.
Decreased proprioception and vibration sense.
Motor
Weakness
Atrophy
36. 36 Complications - long term Neuropathies - central and autonomic
orthostatic hypotension
gastrointestinal atony (lack of normal tone or strength)
atonic urinary bladder
impotence
impairment of special senses
37. 37 Complications - long term Nephropathy
Glomerulosclerosis (arteriolonephrosclerosis)
Thickened basement membrane in glomerulus
Causes microalbuminuria (300 mg / day)
Nodular scarring and destruction of glomerulus. Kimmelstiel - Wilson lesion. Pathognomonic for diabetes mellitus.
38. 38 Complications - long term Retinopathy
Leading cause of blindness. DM has increased risk for cataracts and glaucoma
Pathogenesis:
new vessels, fragile vessels, microaneurysms, hemorrhage. Followed by scarring and retinal detachment. Takes 20 years to develop. 100% of Type 1; 60% Type 2. Need to evaluate eyes yearly. Retinal photos are excellent.
39. 39 Complications - long term Foot ulcers
Most common reason for hospitalization
Due to impaired circulation (PVD)
Abnormal glycoprotein thickens vessel wall
Chronic hypoxia (glycohgb has > affinity for O2)
Due to neuropathy
Cannot feel pain to prevent injury
Prevention: Wear good closed-toe shoes, white cotton socks, keep feet clean and dry, clip toenails straight across, inspect feet daily.
40. 40
41. 41
42. 42 Complications - long term Infections
Skin: boils and abscesses
Urinary tract infections - quickly spread to kidneys
Osteomyelitis (inflammation of bone)
Infected cuts of extremities
Peridontal disease
Finger and toenail fungus
43. 43 Syndrome XInsulin-Resistance Syndrome Caused by insulin dysregulation
Insensitivity
Exaggerated response (25% of population)
Features:
Increased cholesterol, triglycerides
Hypertension, obesity, DM
Causes:
Diet high in refined CHO, low in fiber, high in saturated fats.
44. 44
45. 45 Diabetes Case Presentation Frank Grimaldi Jr, MSEd, MMS, PA-C, ATC, LAT
46. 46 Case 1 A 24-year old white male present to the flight physician assistant’s office for a routine physical. He has been taking flying lessons and is applying for a pilot’s license. Regulations state that he must have a physical examination.
Examination discloses a thin male, 74 inches, 140 pounds. Generally, the exam is unremarkable. Routine screening includes a urinalysis, which demonstrates 4+ glycouria.
47. 47 Does this man have Diabetes Mellitus? There is insufficient information to establish a diagnosis. There are other reasons to spill glucose in the urine. You must ask additional questions.
You find out that even though he denies any history of diabetes, he admits to:
Having incessant thirst
Increase hunger
Increase urination
He has lost 15 pounds over the last three months
48. 48 A glucometer reading revealed a glucose of 490 mg/dl
A blood glucose revealed a glucose level of 496 mg/dl. With normal electrolytes and anion gap
Does this patient have diabetes?
49. 49 Three ways to diagnose diabetes mellitus:
Fasting glucose of > 126 mg/dl
Oral glucose tolerance test with a 2 hr value of > 200 and one other value in-between of > 200
Grossly elevated serum glucose with classic signs and symptoms
50. 50 Your patient is in shock. He does not feel ill and has multiple activities planned. What should you do for him? New onset Type 1 diabetics should be admitted because:
He needs to start on insulin
He requires a lot of patient education
51. 51 Case II 32-year old woman who has type 1 diabetes calls you over the weekend. She has been having some nausea and vomiting for the last 24 hours and can not keep solids down. She has been able to keep liquids down. Her last glucometer reading was 261 mg/dl.
She is on a split dose of NPH and regular insulin twice daily. She did not take her morning insulin because a physician had told her never to take her insulin when she is not eating. She ask you for instructions?
52. 52 Many patients do not take their insulin if they are not eating; this is wrong.
It is important for IDDM patients and their providers to learn how to manage “sick days”.
Note that one of the most common reasons for patient to go into DKA is poor management of their diabetes when they are sick.
Insulin should be taken regardless of whether or not they are eating
Adequate carbohydrates should be taken (15 – 20g q2h)
53. 53 The patient can consume regular coke, Sprite, juices @ 4 – 6 oz q2hrs.
They can also have gelatin, crackers, soup
Patients that are sick require more insulin NOT less
The intermediate or long acting insulin should be given
Regular insulin should be given q4h as per a ‘sliding scale’
54. 54 Case III 69-year old white female was in good health until 3 weeks ago, when she suddenly developed severe polyuria, polydipsia and polyphagia. She has lost 20 pounds ( going from 120 to 100) during that period and feels extremely weak. When her daughter brings her to you, in the ED, she is somewhat lethargic. Past medical history reveals HTN (Tx with a small dose of enalapril). There is no history of cardiac disease.
55. 55 Physical Exam reveals a pale, lethargic, confused woman, breathing rapidly.
B/P is 102/72 P 110 Resp 32
Her skin is very dry, bowel sounds are weakly positive
Blood test revealed
Na+ 130 (135 – 145)
K+ 5.1 (3.5 – 5.1)
Glucose 794 ( 70 – 110)
Cl- 104 (95 – 105)
HCO3 3mEq/L (21 – 30)
pH 6.92 (7.35 – 7.45)
pO2 92 mm (80 – 105)
56. 56 What should you do for her? New onset Type 1 diabetics should be admitted because:
She needs to start on insulin
She requires a lot of patient education
57. 57 CASE IV A 37 year old white female has a 20 year history of diabetes mellitus. She has been having difficulty with hypoglycemia in the early morning. She used to be on beef-pork insulin and did not have any problems.
She takes:
Human NPH 16 U am; 8 U pm
Human Regular 8 U am; 3 U pm
58. 58 Blood glucose monitoring reveal:
3am 7am 12pm 5pm
41 66 109 72
47 132 82 100
35 182 134 142
Why is she developing early-morning hypoglycemia?
59. 59 Insulin have different peaks and duration of action.
In this case you must note that animal insulin has a slower peak than human insulin
In this case this lady was advised to move the NPH evening dose to qhs --- which allowed the NPH peak to occur later
To cover the evening problem one should also increase the bedtime regular insulin --- in this case it was increased by 2 U
60. 60 CASE V A 56-year male has a history of type 2 diabetes for 10 years. He is currently on glipizide 20 mg BID and monitors his glucose twice a day. Over the last 2 weeks his fasting glucose were 157 – 278 (average 199); supper values were 145 – 292 (average 212).
61. 61 Yesterday his fasting glucose was 234 and HgA1c was 14.8%
P.E.: B/P 142/90 P 72 Resp. 12 height: 72 inches weight: 212
The rest of the physical was normal with no evidence of retinopathy or neuropathy
What is the best option for this patient?
62. 62 Though this patient may not want to go on insulin …. We have no choice.
He has unacceptably high glucose values
HgA1C confirms the fact that insulin is needed
What do we start him on?
63. 63 Many clinicians start their type 2 that now require insulin on NPH or ultralente and add regular insulin later as needed for a tune – up treatment.
After knowing what it would take to treat this patient --- you may then decide to use pre-mixed insulin.
Should this patient be hospitalized?
No
64. 64 CASE VI A 30-year female has no prior medical problems. As part of a routine obstetric care, she has a glucose screen at 24 weeks. She is given 50-g glucose to drink and a glucose level is obtained 1 hour later. Her results revealed a level of 156 mg (<140)
She is 64 inches tall and weighs 220
What do you do now?
65. 65 You should now order a 3 hr GTT, which they give 100 g of glucose
Her results were
Fasting: 112mg
1hour: 183mg
2hour: 172mg
3hour: 147mg
What is your opinion?
66. 66 This patient has Gestational Diabetes. According to the National Diabetes Data Group – Dx is made if two or more values exceed the norm.
You should start this patient on a ADA 2000 calorie diet, give her a glucometer (she is to take readings four times daily) and see her in a week.
67. 67 You see her back in a week and her glucose log reveal:
Fasting Lunch Supper Bedtime
97 93 115 104
112 101 107 99
101 101 89 122
93 105 102 111
115 112 121 118
99 107 113 105
96 101 117 109
68. 68 What should you do now?
This patient should be started on insulin. Though these level appear good; in pregnancy glucose levels are significantly lower.
Target glucose goals are:
Fasting: 60 – 90
Non-fasting (before breakfast) 60 – 105
After meals: < 120
2am – 6am: >60
69. 69 Since most of these patients seem to be insulin resistant it is recommended to start with 0.6 U/kg/day. In this patient we would give 30 – 32 U NPH (or Longer acting) BID. She returns in four days with the following readings:
Fasting Lunch Supper Bedtime
93 99 97 122
86 100 98 113
74 78 99 107
68 90 79 112
70. 70 How is our patient doing?
These reading show that we still have a problem at bedtime. Therefore, we should add 2 U of regular insulin in the evenings
71. 71
THE END