3. Prevalence of DM
Rank 2000 2030
1 India 31.7 India 79.4
2 China 20.8 China 42.3
3 US 17.7 US 30.3
4 Indonesia 8.4 Indonesia 21.3
5 Japan 6.8 Pakistan 13.9
6 Pakistan 5.2 Brazil 11.3
7 Russian Fed. 4.6 Bangladesh 11.1
8 Brazil 4.6 Japan 8.9
9 Italy 4.3 Philippines 7.8
10 Bangladesh 3.2 Egypt 6.7
Wild et al Diabetes Care 2004
Wang et al NEJM 2010
China 2010- 92.4 million adults
17. Diagnosis
FPG 126 mg/dl
2h PG 200 mg/dl (75 gm anhydrous glucose)
RPG 200 mg/dl with symptoms
Reconfirmation on subsequent days
Limitations
Ensure fasting
Influenced by exercise and activity
Analytical variability
Intra-individual variations
18. Glycated Hb (HbA1c)
Diagnosis of DM
- HbA1c 6.5%
- FPG ≥126mg/dl, RPG > 200 mg/dl with
symptoms
- Confirm with a repeat HbA1c
Prediabetes (IFG, IGT)
- HbA1c 5.7 - 6.4%
19. Glycated Hb (HbA1c)
Single estimation
Any time of the day
Better index of overall glycemic exposure
Substantially less biologic variability
Better pre-analytic stability
Denotes risk of long term complications
Standardized and aligned to the
DCCT/UKPDS
20. Total no. people approached -2368
Included in the study - 2245
123 (non responders), Refused = 48
Out of station = 64, Sickness = 9
Pregnancy = 2
18 Excluded – 2hr PG-Not available
Refused to take glucose = 7, Taken
tea/food and later refused = 5
Under took physical activity = 3
Not available on 2 consecutive visits = 2
Finally evaluable in the study - 2227 - 2245
HbA1c not available = 255
HbA1c available - 1972
Flow summary of study subjects
JCEM, Bhansali et al 2010
24. HbA1c and Pre-diabetes
Both the ADA and IEC
HbA1c cut-offs under-diagnosed the presence of
pre-diabetes in 38% and 64% of these subjects
Bhansali et al. Diab Med Dec 2012
26. At insulin initiation, the average patient had:
5 years with A1C >8%
10 years with A1C >7%
Standard Approaches to Therapy Result in
Prolonged Exposure to Elevated Glucose
Brown JB, et al. Diabetes Care. 2004;27:1535-1540.
Sulfonylurea or
Metformin
Monotherapy
ADA
Goal
<7%
Combination
Therapy
Diet/Exercise
Mean
A1C
at
Last
Visit
Years
Diagnosis 2 3 4 5 6 7 8 9 10
9.6%
9.0%
8.6%
6%
7%
8%
9%
10% Insulin
27.
28. DPP-4=dipeptidyl peptidase-4; T2DM=type 2 diabetes mellitus; TZD=thiazolidinedione
AACE Diabetes Mellitus Clinical Practice Guidelines Task Force. Endocr Pract. 2007; 13 (Suppl 1): 16–34.
American Association of Clinical Endocrinologists:
algorithm for patients with T2DM
Drug-naïve patients
HbA1c 6%–7%
Initiate monotherapy
Metformin, TZD, secretagogues,
DPP-4 inhibitors, α-glucosidase inhibitors
HbA1c 7%–8% Initiate combination therapy
Secretagogue + metformin, TZD, or α-glucosidase inhibitor
TZD + metformin
DPP-4 + metformin or TZD
Secretagogue + metformin + TZD
Fixed-dose combinations
Insulin
As above
Exenatide may be combined with oral therapies in patients
not achieving goals
Patients currently
pharmacologically
treated
HbA1c 8%–10% Intensify combination therapy
To address fasting and postprandial glucose levels
HbA1c >10% Initiate / intensify insulin therapy
Lifestyle
Changes
29. WHAT SHOULD BE TARGETED ?
Fasting plasma glucose
Post prandial glucose
30. Post-prandial
hyperglycaemia
Post-prandial
hyperglycaemia
contributes HbA1c ~1%
B=breakfast; L=lunch; D=dinner.
Adapted from Riddle MC. Diabetes Care. 1990;13:676-686.
Plasma
glucose
(mg/dL)
300
200
100
0
Time of day (h)
6 12 18 24 6
Uncontrolled Diabetes HbA1c 8%
Fasting
hyperglycaemia
Basal hyperglycaemia
contributes ~2%
B
L
D
Normal
HbA1c ~5%
Basal vs Post-Prandial
Hyperglycemia – A1c
36. DPP-IV Inhibitors
Vildagliptin
IC50DPPIV 3nmol/L
DPPIV specificity 32-250
Glucagon ↓ ↓ ↓
Intact GLP-1 levels ↑ ↑
T½ 3 hrs
Metabolism 85%hydrolyzed
in liver
HbA1c reduction 0.4-0.9%
Infections ↑
With insulin Approved
Renal insufficiency Moderate to severe
Hepatic dysfunction Caution
Sitagliptin
18 nmol/L
>2600
↓ ↓
↑
12.4 hr
80% excreted
by kidneys
0.4-0.9%
↑
Not approved
Mild to moderate
Use with caution
Saxagliptin
26 nmol/L
NA
↓ ↓
↑
2 hr
33-60% by kidney
40 -67% hepatic
0.43 – 0.54 %
↑
Not approved
Mild to moderate
Use with caution
37. Linagliptin
New class of DPP-IV inhibitor
Exclusively metabolized through entero-
hepatic route
Safe in renal and liver failure
HbA1c reduction by 0.6-0.8%
Reduces albuminuria independent of
glycemic control
Can be given OD or BID
46. Novel Insulin (Degludec)
Ultra long acting basal insulin- insulin Degludec
Extreme dosing intervals of 8–40 h
Daily injection time of IDeg can be varied without
compromising glycemic control or safety
Less hypoglycemia, particularly nocturnal hypoglycemia
Diabetes care Jan 2013
Feb 12, 2013
FDA rejected approval of Degludec
Need of additional CVS safety data
50. Glucokinase Activator (Piragliatin)
Pre-clinical studies
Increases insulin secretion,
Decreases HGO
Concerns
Hypoglycemia,
Fatty liver,
Hyperlipidemia
Matschinsky F et al Diabetes care 2012
51. GPR 40 Modulator
(TAK 875)
TAK-875 50–200-mg OD
reduced A1C similar to 1
mg glimepiride OD
HbA1c reduction was
0.65%-1.37% with
increasing doses
Kaku K Diabetes Care 2013
52. Stem Cells Dev. 2009 Dec;18(10):1407-16
Efficacy Of Autologous Bone Marrow Derived Stem
Cell Transplantation In Patients With Type 2 Diabetes
Mellitus.
Bhansali A, Upreti V, Khandelwal N, Marwaha N, Gupta V, Sachdeva N,
Sharma RR, Saluja K, Dutta P, Walia R, Minz R, Bhadada S, Das S,
Ramakrishnan S.
PGIMER , Chandigarh,
53. BASELINE PARAMETERS
N=10 (8 men)
Mean age: 57.5± 5.9 years
Mean duration of DM: 14.6 ± 7.5 years
Mean duration of insulin therapy: 5.6 ± 3 years
Mean dose of insulin: 69.4 ± 6.6 units/day
Mean weight : 74.5 ± 11.6 kg
Mean BMI: 26.5 ± 3.4 kg/m2
Mean waist circumference: 93.2 ± 7.8 cm
54.
55.
56. RESULTS
Primary end points
Reduction in insulin requirement by ≥ 50%
Improvement in glucagon stimulated C– peptide
levels at the end of 6 months
Secondary end points
Change in weight, HbA1c and insulin- glucose
homeostasis
Responders :7, Nonresponders:3
61. At 2 years, diabetes remission in no patients in the
medical-therapy group
75% in the gastric-bypass group and
95% in the biliopancreatic-diversion group
NEJM 2012
62. Future
Motto of ADA “Living with diabetes”
With bariatric surgery: “LIVING WITHOUT
DIABETES”
63. Conclusions
Enormous advances have been made in
understanding of the disease , diagnosis and
treatment.
Treatment of diabetes should be tailor-made
and needs to be individualized
Future is pregnant with many possibilities