Type 2 diabetes is a multifactorial disorder characterised by progressive pancreatic beta-cell dysfunction and insulin- resistance, leading to relative insulin deficiency, chronic hyperglycaemia, and various complications. The treatment options for this disorder, which aim at correcting one or other of the two major pathophysiological mechanisms, have been hamstrung by unacceptable side-effects, lack of patient acceptability, and loss of efficacy over time.

1. Type 2 DM / GDM new
updates & guidelines
Dr. Sachin Verma MD, FICM, FCCS, ICFC
Fellowship in Intensive Care Medicine
Infection Control Fellows Course
Consultant Internal Medicine and Critical Care
Ivy Hospital Sector 71 Mohali
Web:- http://www.medicinedoctorinchandigarh.com
Mob:- +91-7508677495

2. INTRODUCTION
Type 2 diabetes is a multifactorial disorder
characterised by progressive pancreatic beta-
cell dysfunction and insulin- resistance,
leading to relative insulin deficiency, chronic
hyperglycaemia, and various complications.
The treatment options for this disorder,
which aim at correcting one or other of the
two major pathophysiological mechanisms,
have been hamstrung by unacceptable side-
effects, lack of patient acceptability, and loss
of efficacy over time.

3. Current Criteria for diagnosis as per
ADA 2010
1. A1C > 6.5%. OR
2. FPG > 126 mg/dl OR
3. two-hour plasma glucose > 200 mg/dl during an OGTT.
OR
4. In a patient with classic symptoms of hyperglycemia or
hyperglycemic crisis, a random plasma glucose> 200
mg/dl
A1C test to be done at least two times a year in patient
meeting treatment goal and quarterly in patients
whose therapy has changed or who are not meeting
glycemic goals.

4. Antiplatelet Therapy in Diabetes
ADA & AHA 2007 recommends aspirin therapy as
primary prevention strategy in those with
diabetes at increased cardiovascular risk which
includes
1. Age > 40 yrs
2. Family history of cardiovascular disease
3. Hypertension
4. Smoking
5. Dyslipidemia
6. Albuminuria

5. • New antiplatelet therapy includes – prasugrel,ticagrelor,
congrelor , elinogel.
• OPTIMUS- 3 trial presented at AHA meeting in 2009
compares the pharmacodynamic effect of 60 mg
loading dose of prasugrel vs. 600 mg loading dose of
clopidogrel in terms of inhibition of platelet
aggregation. Maintenance dose of prasugrel was 10 mg
daily.
• CONCLUSION- Prasugrel have demonstrated superior
antiplatelet activity in diabetes both with respect to
clinical parameter & in terms of inhibition of platelet
aggregation.

6. UPCOMING CHANGES IN MANAGEMENT
GUIDELINES OF DIABETIC KETOACIDOSIS (DKA)
• Use capillary blood ketone measurement instead of
urinay ketone measurement.
• Reduced maintenance fluid rates.In 1st hour administer
2-3 litres of fluid.crystalloids especially 0.9 % normal
saline is the preferred solution.
• Continuation of NS for the first 12 hour of rehydration
• Delay insulin administration until fluid has been
running for an hour.
• Option to continue insulin glargine during treatment.
• Use hypertonic saine instead of mannitol for the
treatment of cerebral oedema(after excluding
electrolyte imbalance).

7. ROUTE OF ADMINISTRATION OF INSULIN
• Continuous infusion through a pump is ideal
• When not available i/m insulin is preferred
over s/c route.
• Insulin through a dripset results in very erratic
administration of insulin as insulin also
attaches to the tubing.

8. RECOMMENDATION FOR THE USE OF ORAL
ANTIDIABETIC AGENT IN PATIENT WITH
DIABETES & RENAL DISEASE

9. CLASS OF DRUG SAFETY PROFILE IN REMARKS
RENAL DISEASE
1ST generation Unsafe risk of prolonged hypoglycemia
sulfonylureas
2nd generation glipizide safe rest unsafe glipizide is preferred.Others to be
sulfonylureas avoided.Risk of hypoglycemia
α -glucosidase Unsafe possible hepatotoxicity
inhibitor
Biguanides unsafe risk of lactic acidosis
Thiazolidinediones Safe volume retention may occur especially
with insulin
Meglitinides repaglinide safe short half life & minimal renal excretion
nateglinide not of repaglinide.
completely safe Significant risk of hypoglycemia with
nateglinide
DPP-4 inhibitors relatively safe dose adjustment needed for moderate to
severe renal disease
amylin analogues safe no dose adjustment required for
moderate to severe renal disease.
no data available for ESRD & dialysis
patient.

10. SITAGLIPTIN DOSE ADJUSTMENT
• Creatinine clearance 50-80 ml/min –100 mg
qd
• Creatinine clearance 30-50 ml/min –50 mg qd
• Creatinine clearance ,30 ml/min or ESRD
(approx. serum cretinine . 3 mg/dl for male &
2.5 mg/dl for women, or on dialysis) –25mg
qd

11. ADVANCES IN THERAPY FOR TYPE 2
DIABETES MELLITUS
INCRETIN GROUP OF DRUGS –
• Glucagon like peptide 1 (GLP 1) receptor agonists.
• Dipeptidyl peptidase 4 (DPP 4) inhibitor.
GLP 1 analog control blood glucose through regulation of
islet function principally with the stimulation of insulin &
inhibition of glucagon secretion . they also inhibit gastric
emptying & reduce food intake leading to weight loss.they
may reduce blood pressure & plasma lipid profile in patient
of type 2 diabetes mellitus leading to decrease in incidence
of cardiovascular event.
Treatment related adverse events include nausea, vomiting
& rarely pancreatitis.marketed as exenatide & liraglutide.

12. DPP 4 inhibitors (gliptins) –GLP 1 has a very short half
life of 2-3 min. due to hydrolysis by DPP 4 .DPP 4
inhibitors enhance & prolong the action of incretin
hormones by competitively antagonizing with the
enzyme DPP 4.they causes modest reduction
inglycated hb of around 0.7 – 1.0 % .they appear to be
well tolerated, low risk of hypoglycemia, donot cause
weight gain , given as once a day oral therapy.adverse
effects includes adverse immunologic reaction, long
term safety data are awaited.
It is indicated in obese patient with type 2 DM in
combination with metform in or glitazone or both.

13. • SODIUM GLUCOSE TRANSPORTER -2 INHIBITORS (SGLT-2
INHIBITORS)- SGLT-2 INHIBITORS are said to act by suppressing the
glucose reabsorption in the S1 segment of the proximal tubules of
the kidney thus enhancing urine glucose excretion. These drugs are
in phase 3 trials.potential theoretical side effects includes urinary
tract & genital tract infections, electrolyte imbalance, increased
urinary frequency, stroke, disturbed sleep
• BROMOCRIPTINE :-USFDA has approved use of a special
formulation of the centrally acting dopamine agonist bromocriptine
either as monotherapy orin conjunction with other antidiabetic
agents. Mechanism of action may involve improvement of glucose
& energy metabolism through activation of central dopaminergic
pathway.

14. DIABETES IN PREGNANCY
Diabetes in pregnancy is classified as
1. Pregestational diabetes which may be typa 1 or type 2 &
2. Gestational diabetes mellitus
DIAGNOSIS OF GDM :-
ADA procedure :-
• ADA recommends two step procedure in step 1, 50 gm glucose
challenge test is used for screening without regards to the time
of last meal or time of the day.In step 2 if 1 hr GCT value is
more than 140 mg/dl than 100gm OGTT is recommended &
plasma glucose is estimated at 0, 1, 2 & 3 hours.GDM is
diagnosed if any 2 values meet or exceed the cutoff values of
95, 180, 155, &140 mg/dl respectively.

15. WHO procedure :-
WHO recommends using a 2 hr 75 gm OGTT with
a threshold plasma glucose concentration of
more then 140 mg/dl at 2hrs, similar to that of
IGT outside pregnancy.
• The introduction of single step procedure for
both screening & diagnosis has made it clear &
simple.