Discussion on Diabetes Mellitus based on 2018 guideline of American Diabetes association. Mainly focusing on oral hypoglycemic agents safety profile.

1. Dr. Md. Mamunul Abedin (Shimul)
Medical Officer
General Hospital, Jamalpur
Presented by:

3. Diabetes mellitus is a clinical
syndrome characterized by an
increase in plasma blood glucose
(hyperglycemia).
Ref: Davidson

4. In 2017,
 approximate 425 million adults (20-79 yrs)
were living with diabetes;
by 2045,
 this will rise to 629 million

5. In 2017,
 Proportion of people with T2DM is increasing in
most countries
 79% of adults with diabetes were living in low-
and middle-income countries
 The greatest number of people with diabetes
were between 40 and 59 years of age
 1 in 2 (212 million) people with diabetes were
undiagnosed
 Diabetes caused at least USD 727 billion
dollars in health expenditure in 2017
 More than 1.1 million children were living with
T1DM

6. In 2017,
How many people died
of Diabetes & High
Blood Glucose?
3.7 millions (WHO)
4 millions (IDF)

7. In 2017,
How Many live births were
affected by diabetes during
pregnancy??
More than 21 millions
(1 in 7 births)

9. CLASSIFICATION
 1. Type 1 diabetes (due to autoimmune b-cell destruction, usually
leading to absolute insulin deficiency)
 2. Type 2 diabetes (due to a progressive loss of b-cell insulin secretion
frequently on the background of insulin resistance)
 3. Gestational diabetes mellitus (GDM) (diabetes diagnosed in
the second or third trimester of pregnancy that was not clearly overt diabetes
prior to gestation)
 4. Specific types of diabetes due to other causes, e.g.,
 Monogenic diabetes syndromes - neonatal diabetes, MODY,
 Diseases of the exocrine pancreas (such as cystic fibrosis and pancreatitis), and
 Drug- or chemical-induced diabetes (such as with glucocorticoid use, in the treatment of
HIV/AIDS, or after organ transplantation)

10. Criteria for the diagnosis of diabetes:
 FPG ≥126 mg/dL (7.0 mmol/L). Fasting is defined
as no caloric intake for at least 8 h.
OR
 2-h PG ≥ 200mg/dL (11.1mmol/L) during OGTT.
OR
 A1C ≥ 6.5% (48 mmol/mol).
OR
 In a patient with classic symptoms of hyper-
glycemia or hyperglycemic crisis, a random
plasma glucose ≥ 200 mg/dL (11.1 mmol/L).

11. Diagnostic Test
 Generally, FPG, 2-h PG during 75-g
OGTT, and A1C are equally appropriate
for diagnostic testing.
 Compared with FPG and A1C cut points,
the 2-h PG value diagnoses more people
with diabetes.

12. A1C
 To avoid misdiagnosis or missed diagnosis, the A1C
test should be performed using a method that is
certified by the NGSP.
 Marked discordance between measured A1C and
plasma glucose levels should raise the possibility of
hemoglobin variants.
 In conditions associated with increased red blood cell
turnover, such as sickle cell disease, pregnancy
(second and third trimesters), hemodialysis, recent
blood loss or transfusion, or erythropoietin therapy,
only Plasma Blood Glucose criteria should be
used to diagnose diabetes.

13. A1C
 Advantages of A1C: compared with the FPG &OGTT
Greater convenience (fasting not required)
Greater pre-analytical stability
Less day-to-day variance during stress and
illness.
 Disadvantages of A1C:
Lower sensitivity
Greater cost
Limited availability of A1C testing in certain
regions
Imperfect correlation between A1C and average
glucose in certain individuals.

14. A1C
 National Health & Nutrition Examination
Survey (NHANES) data indicate that an
A1C cut point of ≥6.5% (48 mmol/mol)
identifies a prevalence of undiagnosed
diabetes that is one-third of that using
glucose criteria.

15. Confirming the Diagnosis:
 Unless there is a clear clinical diagnosis a
second test is required for confirmation.
 If two different tests (such as A1C and FPG)
are both above the diagnostic threshold, this
also confirms the diagnosis.
 If a patient has discordant results from two
different tests, then the test result that is
above the diagnostic cut point should be
repeated.

16. Plasma blood glucose rather than A1C
should be used to diagnose the acute
onset of type 1 diabetes in individuals with
symptoms of hyperglycemia.
Screening for type 1 diabetes with a panel
of auto-antibodies is currently recommen-
ded only in the setting of a research trial.

17. Testing for type 2 diabetes in asymptomatic people should
be considered in adults of any age who are overweight or
obese (BMI ≥23 kg/m2 in Asian Americans) and who have
one or more additional risk factors for diabetes
For all people, testing should begin at age 45 years.
If tests are normal, repeat testing carried out at a minimum
of 3-year intervals is reasonable.
To test for type 2 diabetes, FPG, 2-h plasma glucose during
75-g OGTT, and A1C are equally appropriate.
In patients with diabetes, identify and treat other cardio-
vascular disease risk factors.

18. Test for undiagnosed diabetes at the first prenatal visit in
those with risk factors, using standard diagnostic
criteria.
Test for GDM at 24–28 weeks of gestation in pregnant
women not previously known to have diabetes.
Test women with GDM for persistent diabetes at 4–12
weeks postpartum, using the OGTT and clinically
appropriate non-pregnancy diagnostic criteria.
Women with a history of GDM should have lifelong
screening for the development of diabetes or
prediabetes at least every 3 years.

19. Diagnosis: GDM diagnosis can be accomplished with
either of two strategies.
One-step Strategy
Perform a 75-g OGTT, with plasma glucose measurement
when patient is fasting and at 1 and 2 h, at 24–
28weeks of gestation in women
The OGTT should be performed in the morning after an
overnight fast of at least 8 h.
The diagnosis of GDM is made when any of the following
plasma glucose values are met or exceeded:
Fasting: 5.1 mmol/L
1 hour: 10.0 mmol/L
2 hour: 8.5 mmol/L

20. Two-step Strategy
Step 1: Perform a 50-g GLT (non-fasting),with plasma glucose
measurement at 1 h, at 24–28 weeks of gestation in women
not previously diagnosed with overt diabetes. If the plasma
glucose level measured 1 h after the load is ≥ 7.2-
7.8mmol/L, proceed to a 100-g OGTT.
Step 2: The 100-g OGTT should be performed when the
patient is fasting. The diagnosis of GDM is made if at least
two of the following four plasma glucose levels are met or
exceeded:
Fasting: 5.8 mmol/L
1 hour: 10.6 mmol/L
2 hour: 9.2 mmol/L
3 hour: 8.0 mmol/L

21. A1C Goals:
A reasonable A1C goal for many non-pregnant adults is 7%
More stringent A1C goals (6.5% ) for selected patients without
significant hypoglycemia or polypharmacy. Appropriate
patients : short duration of diabetes, type 2 diabetes treated
with lifestyle or metformin only, long life expectancy, or no
significant cardiovascular disease.
Less stringent A1C goals (8%) for patients with a h/o severe
hypoglycemia, limited life expectancy, advanced
microvascular or macrovascular complications, extensive
comorbid conditions, or long-standing diabetes in whom the
goal is difficult to achieve.

22. Most people with type 1 diabetes should be treated with
multiple daily injections of prandial insulin and basal insulin
or continuous subcutaneous insulin infusion.
Most individuals with type 1 diabetes should use rapid-acting
insulin analogs to reduce hypoglycemia risk.
Individuals with type 1 diabetes who have been successfully
using continuous subcutaneous insulin infusion should
have continued access to this therapy after they turn 65
years of age.

23. Insulin is the mainstay of therapy for individuals with T1DM.
Generally, the starting insulin dose is based on weight, with
doses ranging from 0.4 to 1.0 units/kg/day.
In one study, Metformin was found to reduce insulin
requirements (6.6 units/day) and led to small reductions in
weight and total and LDL cholesterol.
Surgical Treatment For Type 1 Diabetes:
Pancreas and Islet Transplantation

24. At diagnosis,
initiate lifestyle Mx, Set A1C target and initiate
pharmacologic therapy.
At diagnosis,
if A1C is < 9%, Consider Monotherapy
if A1C is ≥ 9%, Consider Dual Therapy
if A1C is ≥10%, Blood glucose is ≥ 16.67 mmol/L, or Pt
is markedly symptomatic, Consider Combination
Injectable Therapy.

25. Monotherapy : Lifestyle Mx +
Metformin
Metformin, if not contraindicated and if tolerated, is
the preferred initial pharmacologic agent for the
treatment of type 2 diabetes.
Long-term use of metformin may be associated
with biochemical vitamin B12 deficiency, and
periodic measurement of vitamin B12 levels
should be considered in metformin-treated
patients, especially in those with anemia or
peripheral neuropathy.

26. Dual Therapy : Lifestyle Mx +
Metformin +
One Additional agent
ASCVD ??
If Yes,
Add agent proven to reduce major adverse CV events
and/or CV mortality.
If No,
Add second agent after consideration of drug-specific
effects and patient factors.

27. Triple Therapy: Lifestyle Mx +
Metformin +
Two Additional agent
Add Third agent based on drug-specific
effects and patient factors.

28. Class Efficacy Hypoglyc
emia
Weight
Change
ASCVD CHF Renal
Effects
Metformi
n
High No Modest
Loss
Potential
Benefit
Neutral Contraind
icated in
eGFR <
30
SGLT-2
Inhibitors
Intermedi
ate
No Loss Benefit Benefit Not
recomme
nded in
eGFR <
60
GLP-1 RA High No Loss Benefit:
Liraglutid
e
Neutral Not
indicated
in eGFR <
60

29. Class Efficacy Hypogl
ycemia
Weight
Chang
e
ASCVD CHF Renal Effects
DPP-4
inhibitors
Inter
mediate
No Neutral Neutral Potentia
l risk
with
Saxa+Al
ogliptine
Can be used in
Renal
Impairment
Thiazolidi
nediones
High No Gain Potential
Benefit :
Pioglitazo
ne
Inreased
risk
Generally not
recommended
in renal
impairment due
to fluid
retention
Sulphony
lureas
High Yes Gain Neutral Neutral Not
recommended

30. Class Compoud Renal Dosing Recommendations
Biguanides Metformin No dose adjustment if eGFR < 45,
discontinue if eGFR < 30
Sulfonylureas Glipizide
Glimepiride
Avoid use in patients with renal impairment
Thiazolidinedi
ones
Pioglitazone
Rosiglitazone
No dose adjustment required
DPP-4
inhibitors
Sita+Saxa+Al
o
Linagliptin
Dose adjustment required
No dose adjustment required
SGLT 2
inhibitors
Canagliflozin
Dapagliflozin
Empagliflozin
Dose adjustment required
Contraindicated with eGFR < 30
GLP-1 RA Exenatide Contraindicated with eGFR < 30

31. Discussions??

32. Which one is better
OHA in Add-on
Therapy????

33. Thank
You

34. Hypertension
 All hypertensive patients with diabetes should
monitor their blood pressure at home.
 BP goal in most patients: below 140/90mmHg
 BP goal in High Risk patients: 130/80mmHg
 In Pregnant Diabetic & Hypertensive patients:
120-160/80-105mmHg
 Initial treatment for HTN should include any of
the drug classes : ACE inhibitors or ARBs,
thiazide-like diuretics, or CCB

37. LIPID MANAGEMENT
 For patients of all ages with diabetes and athero-
sclerotic cardiovascular disease, high-intensity
statin therapy (Atorvastatin 40–80 mg) should be
added to lifestyle therapy.
 Ages below 40 with CV disease and Ages above
70 without CV diseases may be provided with
moderate -intensity statin therapy (Atorvastatin
10–20 mg, Rosuvastatin 5–10 mg)