This document provides an overview of diabetes mellitus including definitions, classification, epidemiology, pathophysiology of type 1 and type 2 diabetes, and goals of treatment. Key points include: - Type 1 diabetes results from autoimmune destruction of pancreatic beta cells in genetically predisposed individuals and requires lifelong insulin treatment. - Type 2 diabetes involves both insulin resistance and impaired insulin secretion and is strongly associated with obesity and physical inactivity. It can often be managed through lifestyle modifications and oral medications. - Medical nutrition therapy, physical activity, weight loss (if indicated), glucose monitoring, and pharmacologic therapy including insulin are important components of diabetes management and prevention of complications.

1. Week
Diabetes Mellitus
2
Part I
Anas Bahnassi PhD CDM CDE

2. Lecture Outline
Definition, Classification, and Epidemiology
Carbohydrate Metabolism
Type -1 Diabetes
Type-2 Diabetes
Gestational Diabetes
Long-term complications type-2
Prevention of type-1 and type 2 diabetes
Medical Nutrition Therapy
Pharmacologic Therapy

3. Definition, Classification, and Epidemiology
A relative or an absolute lack of insulin
Clinical characteristics are symptomatic glucose intolerance resulting in hyperglycemia and
alterations in lipid and protein metabolism.
Over the long term, these metabolic abnormalities contribute to the
development of complications such as retinopathy, nephropathy, and
neuropathy.
Most cases of diabetes mellitus can be assigned to type 1 or type 2
diabetes.
Gestational diabetes describes glucose intolerance that has its onset
during pregnancy.
Subclinical glucose intolerance or “prediabetes” is identified as impaired
fasting glucose (IFG) and/or impaired glucose tolerance (IGT).

4. Definition, Classification, and Epidemiology
Type 1 and Type 2 Diabetes
Type 1
Characteristics
Other names
Percentage of
diabetic population
Age at onset
Pancreatic function
Pathogenesis
Previously, type I; insulin-dependent
diabetes mellitus (IDDM); juvenile-onset
diabetes mellitus
5–10%
Usually <30 yr; peaks at 12–14 yr; rare
before 6 mo; some adults develop type 1
during the fifth decade
Usually none, although some residual Cpeptide can sometimes be detected at
diagnosis, especially in adults
Associated with certain HLA types; presence
of islet cell antibodies suggests autoimmune
process
Type 2
Previously, type II; non–insulin-dependent diabetes
mellitus (NIDDM); adult-onset diabetes mellitus
90%
Usually >40 yr, but increasing prevalence among
obese children
Insulin present in low, “normal,” or high amounts
Defect in insulin secretion;
tissue resistance to insulin;
↑ hepatic glucose output

5. Definition, Classification, and Epidemiology
Type 1 and Type 2 Diabetes
Type 1
Characteristics
Family history
Obesity
History of
ketoacidosis
Clinical
presentation
Treatment
Type 2
Generally not strong
Strong
Uncommon unless “overinsulinized”
with exogenous insulin
Often present
Common (60–90%)
Moderate to severe symptoms that
generally progress relatively rapidly
(days to weeks): polyuria, polydipsia,
fatigue, weight loss, ketoacidosis
Insulin
MNT
Physical activity
Amylin mimetic (pramlintide)
Mild polyuria, fatigue; often diagnosed on routine physical or
dental examination
Rare, except in circumstances of unusual stress (e.g., infection)
MNT, Physical activity
Antidiabetic agents (biguanides, nonsulfonylurea insulin
secretagogues, sulfonylureas, thiazolidinediones, α-glucosidase
inhibitors, incretin mimetics/analogs, DPP-4 inhibitors)
Insulin, Amylin mimetic (pramlintide)

6. Definition, Classification, and Epidemiology
Type 1 Diabetes
(a)5% to 10% of the diagnosed diabetic
population has type 1 diabetes
(b)It usually results from autoimmune
destruction of the pancreatic β-cells.
(c)Little or no pancreatic reserve, tendency
to develop ketoacidosis, and require
exogenous insulin to sustain life.
(d)The incidence of autoimmune-mediated
type 1 diabetes peaks during childhood
and adolescence, but can occur at any
age.
Type 2 Diabetes
(a) Type 2 diabetes is the most prevalent
(b) Heterogeneous disorder that is
characterized by
(a) Obesity,
(b) β-cell dysfunction,
(c) Resistance to insulin action,
(d) increased
hepatic
glucose
production.
(c) Incidence and prevalence of diabetes
increase dramatically with age.

7. Carbohydrate Metabolism (post-prandial)
Food
Digested
Inhibits hepatic glucose
production by
suppressing glucagon
and its effects.

Glucose
Conc.
Insulin
Released
Glucose is converted
to free fatty acids and
stored as
triglycerides.
Stimulates the
uptake of amino
acids and their
conversion to protein
The liver does not require
insulin for glucose transport,
but insulin facilitates the
conversion of glucose to
glycogen and free fatty acids.
The latter are esterified to
triglycerides, which are
transported by very-lowdensity lipoproteins (VLDLs)
to adipose and muscle tissue.

8. Carbohydrate Metabolism (fasting)
Fasting

Glucose
Conc.
Min.
Glucose
for CNS
Other
Hormones
Released
Glycogen
to
Glucose
Insulin
Release
Inhibited
Amino
acids to
glucose
TG to
Fatty
Acids

9. Type-1 Diabetes
Postprandial is first
affected then
fasting levels
affected when 8090% of β-cells are
destroyed
Autoimmune
destruction of β-cells
triggered by
environmental factors
(Virus, Toxin).
Pathogenesis
 Immediate or
first phase insulin
response BUT
glucose remains
normal
Antigens
(human leukocyte
antigen [HLA]-DR3
or HLA-DR4), and
circulating insulin
antibodies.
Asypmtomatic
period during βcells destruction

10. Type-1 Diabetes
Treat with insulin
Blurred vision
due to
osmotic
changes in the
lens
Glucose
provides an
excellent
medium for
infections
Insulin
secretion
compromised
Progressive
fasting
hyperglycemia
occurs
Clinical
Presentation
Ketonemia,
ketonuria,
and,
ultimately,
ketoacidosis
Weight loss,
metabolism of
glycogen and
fatty acids to
ketones
Gluc. Conc.>
180 mg/dL,
glucosuria
osmotic
diuresis
Symptoms of polyuria
with compensatory
polydipsia appear

11. Type-1 Diabetes
Honeymoon Period
Decreased blood glucose concentrations and markedly decreased insulin
requirements.
Lasts weeks… up to a year
Increasing exogenous insulin requirements are inevitable
and should be anticipated.
During this time, patients should be maintained on
insulin even if the dose is very low, because interrupted
treatment is associated with a greater incidence of
resistance and allergy to insulin .

12. Type-2 Diabetes
Impaired insulin
secretion and
resistance to insulin
action.
Factors such as
obesity and a
sedentary lifestyle
also contribute to
the development of
insulin resistance
Pathogenesis
Stronger
association with FH,
no relation with
HLA circulating ICA
s are absent
Impaired glucose
utilization,
increased hepatic
glucose production,
and excess glucose
accumulates in the
circulation
The pancreas
produces more
insulin in an
attempt to
overcome insulin
resistance

13. Type-2 Diabetes
Basal insulin levels are
typically normal or
elevated at diagnosis.
β-cells lose their
ability to respond to
 glucose conc.
leading to  insulin
secreted and
insulin resistance is
worsened
Pathogenesis
Early-phase insulin
release in response
to glucose often is
reduced resulting in
postprandial
hyperglycemia
Insulinotropic
substances such as
incretin hormones
levels are altered.
Evidence suggests that
decreased peripheral
glucose uptake and
utilization in muscle is
the primary site of
insulin resistance and
results in prolonged
postprandial
hyperglycemia

14. Metabolic Syndrome
Genetic
Predisposition
Environmental
factors:
Obesity
Age
Sedentary lifestyle
β-cells
Defect
IFG, IGT,
Diabetes
type-2
Lipid Disorder
HTN,
Stroke
Insulin
Resistance
Increased
Insulin
Secretion
CVD
Other
Conditions

15. Type-2 Diabetes
Symptoms
are mild and
gradual
Fatigue,
polyurea,
polydipsia,
but no
ketosis.
Insulin maybe
needed for
many
Treat with
MNT, phys
activity, oral
antidiabetic
Clinical
Presentation
Microvascular
complications
at diagnosis
 7-10 yrs
undiagnosed
diabetes

endogenous
insulin
promote
lipogenesis 
weight loss
not common.
Enough insulin to prevent
lipolysis
Macrovascular
disease is
evident at
diagnosis

16. Normal and diabetic glucose levels
Normal
Fasting
<100 (5.6)
½, 1, 1½ hr
<200 (11.1)
2 hr
<140 (7.8)
Impaired glucose tolerance
<126 (7.0)
≥200 (11.1)
140–200 (7.8–11.1)
≥200 (11.1)
≥200 (11.1)
Impaired fasting glucose
Diabetes (nonpregnant adult)
100–125 (5.6–6.9)
≥126 (7.0)

17. Diagnosis criteria –Diabetes Mellitus
(1) Classic signs and symptoms of diabetes (polyuria,
polydipsia, ketonuria, and unexplained weight loss)
combined with a random plasma glucose ≥200
mg/dL (11.1 mmol/L).
(2) A FPG ≥126 mg/dL (7.0 mmol/L). Fasting means no
caloric intake for at least 8 hours.
(3) After a standard oral glucose challenge (75 g
glucose for an adult or 1.75 g/kg for a child), the
venous plasma glucose concentration is ≥200 mg/dL
(11.0 mmol/L) at 2 hours and >200 mg/dL (11.0
mmol/L) at least one other time during the test
(0.5, 1, 1.5 hours); this is the OGTT.

18. Diagnosis criteria –Diabetes Mellitus
Individuals with FPG values or OGTT values that are intermediate between
normal and those considered diagnostic of diabetes are considered to have
“prediabetes” or IFG or IGT. The categories of FPG values are as follows:
a) A normal FPG is <100 mg/dL (5.6 mmol/L).
b) An FPG of 100 to 125 mg/dL (5.6–6.9 mmol/L) is IFG.
c) An FPG ≥126 mg/dL (7.0 mmol/L) indicates a
provisional diagnosis of diabetes that must be
confirmed, as described.
The corresponding categories when the OGTT is used for diagnosis are as follows:
a) A 2-hour postload glucose (2-hPG) <140 mg/dL (7.8 mmol/L) indicates normal glucose tolerance.
b) A 2-hPG ≥140 mg/dL (7.8 mmol/L) and <200 mg/dL (11.1 mmol/L) indicates IGT.
c) A 2-hPG ≥200 mg/dL (11.1 mmol/L) indicates a provisional diagnosis of diabetes, which must be
confirmed by a second test.

19. Risk Factors for Type 2 Diabetes Mellitus
Adults
Children
Overweight (≥25 kg/m2)
Physical inactivity
Overweight (BMI >85th percentile for age and sex;
or weight >120% of ideal for height)
Family history of diabetes (first- or second-degree
relative)
Ethnic predisposition
Ethnic predisposition
Family history of diabetes (first-degree relative)
Previous IFG or IGT
History of PCOS, GDM, or macrosomia
Maternal history of diabetes (including GDM)
Clinical conditions associated with insulin resistance Signs of insulin resistance (e.g., acanthosis nigricans)
(e.g., severe obesity and acanthosis nigricans)
Hypertension (≥140/90 mmHg or on antihypertensive
therapy)
Conditions associated with insulin resistance (e.g.,
Dyslipidemia
hypertension, dyslipidemia, or PCOS)
• HDL-C <35 mg/dL (0.90 mmol/L)
• Triglyceride >250 mg/dL (2.82 mmol/L)
• CVD

20. Goals of therapy (American Diabetes Association)
Monitoring
Parameter
Fasting plasma
glucose
2 hr postprandial
plasma glucose
2–4 am plasma
glucose
HbA1c
Urine ketones
School Age
(6–12 years)
(mg/dL)
90–180
Adolescents and
Young Adults
(13–29 years)
Pregnancy
(mg/dL)
(mg/dL)
90–130
60–90
Not routinely
recommended
100–180
Not routinely
recommended
90–150
≤120
<7.0%
<8.0%
Absent to rare Absent to rare
<7.5%
Absent to rare
5–6%
Rare
Adults
(mg/dL)
70–130
<180
>70
>60

21. ADA lipids goals for adults
Low-density lipoproteins
<100 mg/dL (<2.6 mmol/L)
Triglycerides
<150 mg/dL (<1.7 mmol/L)
High-density lipoproteins
• Men
• Women
>40 mg/dL (>1.0 mmol/L)
>50 mg/dL (>1.3 mmol/L)
More stringent goals (i.e.,
<70 mg/dL [1.8 mmol/L])
may be considered for
individuals with overt
cardiovascular disease

22. A case approach understanding
R.P. is a 43-year-old woman visiting the drop-in
clinic to obtain a routine physical examination
for her new job.
PMH
Significant for GDM.
was told (last child born 3 years ago) that she
had “borderline diabetes,” which resolved each
time after giving birth.
FH
Significant for type 2 diabetes hypertension, and
CVD.

23. A case approach understanding
Medications
denies tobacco or alcohol use.
SH
She tries to walk 15 minutes twice a week.
Had her last baby 3 yrs ago.
PE
Significant for moderate central obesity (5 feet 4
inches; 160 lbs; BMI, 30.2 kg/m2), BP 145/85
mmHg. R.P. denies any symptoms of polyphagia,
polyuria, or lethargy.
She has documented hypertension and an FPG
value of 119 mg/dL, measured 2 months prior.

24. A case approach understanding
What features of R.P.'s history and examination are consistent
with an increased risk of developing type 2 diabetes?
1. Age
2. Ethnicity
3. Weight
4. Family history of diabetes
5. History of GDM
6. Documented IFG.
Type 2 diabetes is also associated with other
disorders such as hypertension.
R.P. has not controlled hypertension and a family
history of hypertension and CVD
may indicate that she is predisposed to insulin
resistance

25. A case approach understanding
The physician orders another FPG for R.P., which comes back at
122 mg/dL. How should R.P. be managed at this time?
1. Education about risk for developing type 2 diabetes.
2. Institute lifestyle modifications (MNT, physical
activity) aiming to lose weight, improve her CV
health, and decrease her risk for developing
diabetes.
3. A weight loss goal of 5% to 10%
4. Increase her level of moderate physical
activity to at least 150 minutes/week.
5. Manage hypertension managed.
6. Metformin to prevent the development of
type 2 diabetes is not recommended.

26. Treatment of Diabetes
1. Medical Nutrition Treatment (MNT)
2. Drugs (Insulin, oral hypoglycemic agents)
3. Exercise

27. Medical nutrition therapy
Nutrition therapy is designed to help patients achieve appropriate
metabolic and physiological goals. Unfortunately, patient acceptance and
adherence to diet and meal planning is often poor.
Type I diabetes
Type 2 diabetes
Adequate carbohydrates timed to
match the peak of insulin
Emphasize normalizing plasma
glucose and lipid levels and
maintain normal BP to prevent CVD
Regularly scheduled meals and snacks
are required to prevent hypoglycemic
reactions
A sustainable weight loss of 5% to
7% can be achieved through a
structured programs that
emphasize lifestyle changes,
physical activity, and food intake
that modestly reduces caloric and
fat intake
Patients who can “count
carbohydrates” can inject rapid- or
short-acting insulin matching their
anticipated intake.

28. Exercise
A key factor in the treatment of diabetes, particularly type 2.
Obesity and inactivity contribute to the development of glucose
intolerance in genetically predisposed individuals.
Regular exercise reduces cholesterol, BP, weight, need for insulin or other agents,
enhances insulin sensitivity, and improves psychological well-being by reducing stress.
These effects are mediated through norepinephrine, epinephrine, growth
hormone, cortisol, and glucagon, along with the suppression of insulin secretion

29. Overall goals of treatment
Prevent acute and chronic complications.
Periodic assessments of HbA1c coupled with regular measurement of fasting,
preprandial, and postprandial glucose levels should be utilized to assess therapy.
(1) Strive for glycemic control achieved.
(2) Keep patients symptoms free.
(3) Maintain normal growth and development in
children.
(4) Eliminate or minimize other cardiovascular risk
factors.
(5) Integrate the patient into the healthcare team.

30. Method of monitoring glycemic control
(1) Urine ketone testing.
(1) More recommended for type 1.
(2) Should be checked when glucose level >300mg/dL (16.7mmol/L)
(2) Plasma glucose (FPG, PPG)
(1) Whole blood glucose (mg/dL) = Plasma glucose (mg/dL) ÷ 1.12
(2) Plasma glucose (mmol/L) = Plasma glucose (mg/dL) ÷ 18
(3) Self monitoring blood glucose.
(1)
(2)
(3)
(4)
In type 1: correlate meals, exercise, and insulin dose.
Pregnant women may have over control problems.
Protect from hypoglycemia episodes.
A must for intensive therapy patients.

31. Method of monitoring glycemic control
(1) Continuous glucose monitoring.
(2) Glycosylated hemoglobin.
(1) It has become the gold standard for measuring chronic
glycemia and is the clinical marker for predicting longterm complications, particularly microvascular
complications.
(2) It is the least affected by recent fluctuations in blood
glucose.
(3) measures the percentage of hemoglobin A that has been
irreversibly glycosylated at the N-terminal amino group
of the β-chain.
(4) Alterations in RBC survival such as hemoglobinopathies,
anemias, acute or chronic blood loss, and uremia may
affect HbA1c values, resulting in inaccurate indications of
glycemic control. Antioxidants such as vitamins C and E
also may interfere with the glycosylation process

32. Factors affecting HbA1c
Alterations in RBC Survival
Hemoglobinopathies
Anemias
Hemolytic
Iron deficiency
Blood loss
Decreased
Decreased
Decreased
Decreased
Assay Interference
Uremia
Hemodialysis
Antioxidants
Increased or no change
No change
Decreased

33. Physical and Chemical Properties of Human Insulin
21 amino acids
α-chain
β-chain
30 amino acids
Monomers
Dimers
Zn++
Zn++
Self-aggregation
in solution
Hexamers
(around Zn2+)

34. Rapid acting insulin
Brand
Onset
min
Peak min
Duration
hr
Humalog or lispro 15-30
30-90
3-5
Novolog or aspart 10-20
40-50
3-5
Apidra or glulisine 20-30
30-90
1-2½
Role in glucose
management
Rapid-acting insulin
covers insulin needs for
meals eaten at the same
time as the injection.
This type of insulin is
often used with longeracting insulin.

35. Primary Structure of Lys(B28), Pro(B29)–Insulin
Insulin
Gly
23
Lispro
Gly
Glu
24
Glu
Phe
25
Phe
Tyr
26
Thr
27
Tyr
28
Thr
Pro
Lys
29
30
Lys
Pro
Thr
Thr

36. Primary Structure of Asp(B28)-Insulin
Insulin
Gly
23
Aspart
Gly
Glu
24
Glu
Phe
25
Phe
Tyr
26
Thr
27
Tyr
28
Thr
Pro
Lys
29
30
Asp
Lys
Thr
Thr

37. Primary Structure of Glu(B29), Lys(B3)–Insulin
Insulin
Phe
1
Glulisine
Phe
Val
Asn
Gln
Pro
Lys
Thr
2
3
4
28
29
30
Val
Lys
Gln
Pro
Glu
Thr

38. Asp
Heinmann et al. Diabet. Med.
1996
Lys Pro
Glu
Lys
38

39. Short acting insulin
Brand
Regular (R)
humulin or
Actarapid
Onset
Duration
Peak hr
min
hr
30-60
2-5
5-8
Velosulin (for
use in the insulin 30-60
pump)
2-3
2-3
Role in glucose
management
Short-acting insulin
covers insulin needs
for meals eaten within
30-60 minutes

40. Intermediate acting insulin
Brand
NPH (N)
Onset
min
1-2
hours
Peak hr
4-12
hours
Duration
hr
Role in glucose
management
Intermediate-acting
insulin covers insulin
needs for about half
the day or overnight.
This type of insulin is
18-24 hours often combined with
rapid- or short-acting
insulin

41. Plasma insulin levels
Action Profiles of Injected Human Insulin
Regular 6–8 hours
NPH 12–20 hours
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24
Hours

42. Long acting insulin
Brand
Onset
min
Peak hr
Duration
hr
No peak
time;
Lantus (insulin
insulin is
1-1½ hour
20-24 hours
glargine)
delivered
at a steady
level
Levemir
(insulin
detemir)
1-2 hours 6-8 hours
Role in glucose
management
Long-acting insulin
covers insulin needs
for about one full day.
This type of insulin is
often combined, when
needed, with rapid- or
short-acting insulin
Up to 24
hours
42

43. Primary Structure of Gly(A21), Arg(B31), Arg(B32)-Insulin
Insulin
A-chain
Leu
Glu
Asn
Tyr
Cys
Asn
16
17
18
19
20
21
Glargine
Leu
Glu
Asn
Tyr
Cys
Gly
Insulin
B-chain
Phe
Tyr
Thr
Pro
Lys
Thr
25
26
27
28
29
30
Glargine
Phe
Tyr
Thr
Pro
Lys
Thr
Arg
Arg

44. Primary Structure of Lys(B29)-N--Tetradecanoyl, Des(B30)-Insulin
Detemir
Gly
Glu
Phe
Tyr
Thr
Pro
Lys
23
Insulin
24
25
26
27
28
29
Gly
Glu
Phe
Tyr
Thr
Pro
• Fatty acid tail (myristic acid) added to
human insulin
• Complexes with albumin>20 hour
action
Lys
Thr
30
Thr
(CH2)4
NH
CO
R
44

45. Glucose infusion rates
(mg/kg/min)
Action Profiles of long acting insulin analogs – Glargine
6
NPH
5
4
Glargine
3
0.4 U/kg
2
Placebo
1
0
0
2
4
6
8
10
12
14
16
Time (h)
18
20
22
24
26
28
30

46. Glucose infusion rate (mg/kg/min)
Action Profiles of long acting insulin analogs – Detemir
2.0
1.5
1.0
Detemir - high
Detemir - low
0.5
0.0
-100
Placebo
100
300
500
700
900
Elapsed time (min)
1100
1300
1500

47. Premixed insulin
Brand
Onset
min
Duration
Peak hr
hr
Humulin 70/30 30
2-4
14-24
Novolin
70/30
30
2-12
Up to 24
Novolog
70/30
10-20
1-4
Up to 24
Role in glucose
management
These products are
generally taken two or
three times a day
before mealtime.

48. Mixed vs. Basal Insulin Regimens
Outcome
Analog mix vs.
Human mix
Analog mix
vs. Long-acting
analogs
Analog mix
vs. “Other
regimens”
Strength of
Evidence
FPG
Similar
Favors long-acting
analog
Unknown
Moderate
PPG
Favors analog
mix
Favors analog mix
Unknown
High
A1c Reduction
Similar
Favors analog mix
Unknown
High
Hypoglycemia
Similar
Favors long-acting
analog
Unknown
High
Weight
Similar
Favors long-acting
analog
Unknown
Moderate
Mortality
Unknown
Unknown
Unknown
Unknown
48

49. A case approach understanding of type-1 diabetes
A.H., a slender, 18-year-old woman who was recently discharged from
the hospital for severe dehydration and mild ketoacidosis
FPG = 190 mg/dL (normal, 70–100)
RPG = 250 mg/dL (normal, 140 to <200).
4 weeks before she was hospitalized,
Moved across country for Symptoms of polydipsia, nocturia
(six times a night), fatigue, and a 12-lb weight loss over this
period, which she attributed to the anxiety.
PMH
Remarkable for recurrent upper respiratory
infections and three cases of vaginal moniliasis
over the past 6 months.

50. A case approach understanding of type-1 diabetes
FH
Negative for diabetes, and she takes no medications.
PE
Within normal limits
Weighs 50 kg and is 5 feet 4 inches tall.
Laboratory results are as follows: FPG, 280 mg/dL (normal, <100);
HbA1c, 14% (normal, 4%–6%); and trace urine ketones as
measured by Keto-Diastix (normal, negative).
LR
FPG, 280 mg/dL (normal, <100);
HbA1c, 14% (normal, 4%–6%);
Trace urine ketones (normal, negative).

51. A case approach understanding of type-1 diabetes
Which findings are consistent with type-1 diagnosis in A.H.?
(1) classic symptoms of the disease (polyuria, polydipsia, weight
loss, glucosuria, fatigue, recurrent infections).
(2) A random plasma glucose above 200 mg/dL, and an FPG of
126 mg/dL or higher on at least two occasions.
(3) Elevated HbA1c also is consistent with diabetes mellitus.
(4) Features of A.H.'s history that are consistent with type 1
diabetes include:
(1) Relatively acute onset of symptoms in
association with a major life event
(2) Ketones in the urine,
(3) Negative family history
(4) Relatively young age at onset.

52. A case approach understanding of type-1 diabetes
A.H. will be started on insulin therapy. What are the goals of therapy?
Will normal glucose levels prevent complications?
(1) The goal is to prevent acute and chronic complications.
(2) Physiological insulin therapy involves a complete program of
diabetes management involves a balanced meal plan,
exercise, frequent SMBG, and insulin adjustments based on
these factors.
(3) Lowering blood glucose concentrations through
intensive insulin therapy in persons with type 1
diabetes slows or prevents the development of
microvascular complications (DCCT Study)

53. A case approach understanding of type-1 diabetes
What methods of insulin administration are available to achieve optimal
glucose control?
(1) A physiological insulin regimen is designed to mimic normal insulin secretion as
closely as possible.
(1) Insulin pump therapy (previously referred to as “continuous subcutaneous infusion of insulin”
(2) Basal-bolus insulin regimens consisting of once to twice daily doses of basal insulin coupled
with pre-meal doses of rapid or short-acting insulin

54. Factors Altering Onset and Duration of Insulin Action
(1) Route of administration IV>IM>SC
(2) Factors altering clearance:
(1) Renal function.
(2) Insulin antibodies (IgG).
(3) Hyperthyroidism increases clearance
and insulin action, making insulin
control difficult.
(3) Factors altering SC absorption:
(1) Site of injection
Site
Abdomen
Arm
Hip
Thigh
Half-life absorption (min)
87 ± 12
141± 23
153± 28
164 ± 15
(2) Exercise increases absorption rate.
(3) Heat increases absorption rate.
(4) Massage increases absorption rate.
(5) Smoking is controversial.
(6) Jet injectors increases absorption rate.
(7) Lipohypertrophy delays absorption.
(8) More soluble insulin faster absorption.
(9) Mixtures can mask the regular insulin.
(10)More diluted insulin faster absorption.
(11)Lower doses are absorbed faster.

55. A case approach understanding of type-1 diabetes
How can insulin injections be administered to A.H. in a way that mimics
physiological insulin release?
Long acting insulin
Short acting insulin

56. Estimating Total Daily Insulin Requirements
Type 1 diabetes
Initial dose
0.3–0.5 unit/kg
Honeymoon phase
With ketosis, during illness, during growth
0.2–0.5 unit/kg
1.0–1.5 units/kg
Type 2 diabetes
With insulin resistance
0.7–1.5 units/kg
Estimating basal insulin
Dose need to be adjusted according to SMBG results
Basal requirements vary throughout the day, often increasing during the early
morning hours.
Basal requirements are approximately 50% of total daily insulin needs
The basal requirement also is influenced by the presence of endogenous
insulin, the degree of insulin resistance, and body weight.

57. Estimating Total Daily Insulin Requirements
Estimating premeal insulin
The 500 rule (modified to 450 rule) : 500/total daily dose of insulin
(TDD) = number of carobhydrate grams covered
Using 50 U/day, 500/50 = 10. Therefore, 10 g carbohydrate would be
covered by 1 unit of insulin lispro, glulisine, or aspart.
This role is not quite applicable in type 2 because insulin resistance. It
may underestimate insulin needs
Correction factor
The correction factor determines how far the blood glucose drops per unit
of insulin given and is known as the “1700 rule.” For regular insulin, the
rule is modified to the “1500 rule.”
1700/TDD = point drop in blood glucose per unit of insulin
If a patient uses 28 U/day of insulin, their correction factor (or insulin
sensitivity) would be 1700/28 = 60 mg/dL. Therefore, the patient can
expect a 60 mg/dL drop for every unit of rapid acting insulin administered.

58. Patient’s selection criteria for intensive insulin therapy
Type 1, otherwise healthy patients (>7 years of
age)
Women with diabetes who plan to conceive
Pregnant patients with diabetes (pre-existing)
Patients poorly controlled on conventional therapy
(includes type 2 patients)
Technical ability to test blood glucose
concentrations
Intellectual ability to interpret blood glucose
concentrations and adjust insulin doses
appropriately
Access to trained and skilled medical staff to direct
treatment program and provide close supervision

59. Avoid or use intensive insulin therapy cautiously in:
Patients with counter-regulatory insufficiency
β-Adrenergic blocker therapy
Autonomic insufficiency
Adrenal or pituitary insufficiency
Patients with coronary or cerebral vascular disease
Unreliable, noncompliant individuals, including
those who abuse alcohol or drugs and those with
psychiatric disorders

60. Hypoglycemia
Blood glucose concentration <60 mg/dL: Patient may or may not be
symptomatic. Blood glucose <40 mg/dL: Patient is generally symptomatic. Blood
glucose <20 mg/dL can be associated with seizures and coma
Blurred vision, sweaty palms, generalized sweating,
tremulousness, hunger, confusion, anxiety, circumoral tingling, and
numbness.
Nocturnal hypoglycemia:
nightmares, restless sleep, profuse sweating, morning headache,
morning “hangover.” In one study, 80% of patients with nocturnal
hypoglycemia had no symptoms.
Signs and
symptoms
Ingest 10–20 g rapidly absorbed carbohydrate. Repeat in 15–20
min if glucose concentration remains <60 mg/dL or if patient is
symptomatic. Follow with complex carbohydrate/protein snack if
meal time is not imminent.
Treatment

61. A case approach understanding of type-1 diabetes
A.H. was instructed to inject herself with 12 units of Lantus each morning and give 4
units of Novolog with each meal. The initial goal of therapy is to achieve preprandial
blood glucose concentrations of <180 mg/dL and to eliminate symptoms of
hyperglycemia.
Time
7 AM
Glucose
Concentration
(mg/dL)
160–200
Noon
220–260
5 PM
130–180
11 PM
140–180
Occasional 3 AM tests averaged 160 mg/dL
Urine is negative for ketones.
She eats approximately four carbohydrate servings
for breakfast (60 g) and two to four carbohydrate
servings for lunch and dinner (30–45 g).
She feels a bit better, and her weight has stabilized,
but she still urinates two to three times nightly.

62. A case approach understanding of type-1 diabetes
How would you interpret these results, and how should A.H.'s insulin
doses be altered?
(a)
(b)
(c)
(d)
(e)
(f)
Set glycemic goals
Develop recommendations for pharmacologic therapy
Evaluate the effectiveness of pharmacologic therapy,
Instruct patients to interpret and respond to blood glucose patterns
Evaluate the impact of dietary factors on glycemic control
Modify therapy during acute/intercurrent illness or whenever
patients receive medications known to affect glycemic control
(g) Modify the management plan in response to a change in activity
levels
(h) Identify hypoglycemic unawareness

63. Pharmacottherapy
Anas Bahnassi PhD CDM CDE
abahnassi@gmail.com
http://www.twitter.com/abpharm
http://www.facebook.com/pharmaprof
http://www.linkedin.com/in/abahnassi