1) Prediabetes is a condition where blood sugar levels are higher than normal but not high enough for a diagnosis of diabetes. It affects an estimated 14% of people in India and 9.9-25% of people in other countries. 2) Lifestyle changes like diet modification, increased physical activity, weight loss and smoking cessation can help prevent or delay progression from prediabetes to diabetes. Medications like metformin have also shown effectiveness. 3) People with prediabetes have an increased risk of cardiovascular diseases like heart attack and stroke, even at blood sugar levels below the prediabetes threshold. Intensive lifestyle interventions or metformin treatment can significantly reduce risk of developing diabetes.

1. PRE-DIABETES: A NEW
APPRAISAL
DR. SOMNATH MUKHOPADHAY

2. DEFINITION

3. REF- World Health Organization. Definition and diagnosis of diabetes mellitus and intermediate and hyperglycaemia. (June 14 2019).

4. OCCURRENCE
• According to National Urban Diabetes Survey, the estimated prevalence of
prediabetes is 14 per cent in India.
• 9.9% and 11% according to WHO criteria ( narrower criteria of FPG 110 to 125
mg/dl) in the ESTEBAN French survey and in an English national cohort.
• 25% and 23.9% according to ADA criteria in Luxembourg and in South Korea.

7. RISK ASSOCIATION IN CHILDREN
• Type 2 diabetes is becoming more common in children and adolescents, likely due to the rise in childhood obesity.
• The ADA recommends prediabetes testing for children who are overweight or obese and who have one or more other
risk factors for type 2 diabetes, such as:
1. Family history of type 2 diabetes
2. Being of a race or ethnicity associated with an increased risk
3. Low birth weight
4. Being born to a mother who had gestational diabetes
• The ranges of blood sugar level considered normal, prediabetes and diabetes are the same for children and adults.
• Children who have prediabetes should be tested annually for type 2 diabetes — or more often if the child experiences
a change in weight or develops signs or symptoms of diabetes, such as increased thirst, increased urination, fatigue
or blurred vision.

8. PATHOPHYSIOLOGY
• Increased body weight gain, insulin resistance and beta cell dysfunction are the
most important pathophysiology for both : NGT to prediabetes and prediabetes
to T2DM.
• Beta cell failure and insulin resistance develop concurrently.
• Other factors are : Loss of beta cell volume, increased lipolysis, decreased
endogenous GLP-1, Poor incretin action, inadequate postprandial control of
glucagon secretion and hepatic glucose overproduction.

9. PATHOPHYSIOLOGY

10. THE ELEVATED RISK OF CAD STARTS AT GLUCOSE LEVELS BELOW
THE CUT-OFF POINT FOR PRE-DIABETES AND INCREASES WITH
INCREASING GLUCOSE LEVELS
REF- 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: The Task Force for diabetes, pre-diabetes, and
cardiovascular diseases of the European Society of Cardiology (ESC) and the European Association for the Study of Diabetes (EASD), European Heart Journal, Volume 41, Issue 2, 7
January 2020,

11. CARDIOVASCULAR CONSEQUENCES
• Macrovascular diseases like CVD, stroke and PVD are well associated with prediabetes.
• MI, CHF and atherosclerosis are usual CV associations.
• EPIC- Norfolk study showed 1% increase in HbA1c within normal range is a/w
increased 10 years mortality.
• HbA1c between 6.0 & 6.5% is associated with a 1.5 to 1.7 fold increased risk of
ASCVD.
• Paris prospective cohort showed doubling of CVD mortality in IGT compared to NGT.
• Remarkably prediabetes state is associated with nearly 3 fold higher prevalence of
unrecognized MI than NGT state in Multi Ethnic Study of Atherosclerosis (MESA) Study.

12. LIFE STYLE MODIFICATION 1
• Eat healthy foods. A diet high in fruits, vegetables, nuts, whole grains and olive
oil is associated with a lower risk of prediabetes. Choose foods low in fat and
calories and high in fiber. Eat a variety of foods to help you achieve your goals
without compromising taste or nutrition.
• Be more active. Physical activity helps you control your weight, uses up sugar
for energy and helps the body use insulin more effectively. Aim for at least 150
minutes of moderate or 75 minutes of vigorous aerobic activity a week, or a
combination of moderate and vigorous exercise.

13. LIFE STYLE MODIFICATION 2
• Lose excess weight. In overweight patients, losing just 5% to 7% of their body
weight — about 6.4 kg if BW is 91 kg— can significantly reduce the risk of type 2
diabetes. To keep BW in a healthy range, focus must be made on permanent
changes to eating and exercise habits.
• Stop smoking. Stopping smoking can improve the way insulin works, improving
your blood sugar level.
• Take medications as needed. Metformin may be given in some selected cases.
Medications to control cholesterol and high blood pressure might also be
prescribed.

14. 4.8
7.8
11
0
2
4
6
8
10
12
T2DM INCIDENCE IN THE DIABETES PREVENTION
PROGRAM
Intensive lifestyle
intervention*
(n=1079)
T2DM
incidence
per
100
person-years
Placebo
(n=1082)
Metformin
850mg BID
(n=1073)
58%
31%
*Goal: 7% reduction in baseline body weight through low-calorie, low-fat diet and ≥150 min/week moderate intensity exercise.
IGT, impaired glucose tolerance; T2DM, type 2 diabetes mellitus.
DPP Research Group. N Engl J Med. 2002;346:393-403.

15. 11.6
10.8 10.8
6.7
7.6
9.6
6.2
4.7
3.1
0
2
4
6
8
10
12
14
25-44 45-59 ≥60
Placebo
Metformin
Lifestyle
EFFECT OF AGE ON INCIDENCE OF T2DM IN THE
DPP
T2DM
incidence
per
100
person-years
48%
59%
Age (years)
71%
*Goal: 7% reduction in baseline body weight through low-calorie, low-fat diet
and ≥150 min/week moderate intensity exercise.
DPP, Diabetes Prevention Program;.
DPP Research Group. N Engl J Med. 2002;346:393-403.

16. 9 8.9
14.3
8.8
7.6
7.0
3.3 3.7
7.3
0
2
4
6
8
10
12
14
16
22 to <30 30 to <35 ≥35
Placebo
Metformin
Lifestyle
EFFECT OF WEIGHT ON T2DM INCIDENCE IN THE
DPP
T2DM
incidence
per
100
person-years
65%
BMI (kg/m2)
51%
61%
*Goal: 7% reduction in baseline body weight through low-calorie, low-fat diet
and ≥150 min/week moderate intensity exercise.
DPP, Diabetes Prevention Program.
DPP Research Group. N Engl J Med. 2002;346:393-403.

17. DPP, Diabetes Prevention Program; T2DM, type 2 diabetes mellitus.
DPP Research Group. Lancet. 2009;374:1677-1686.
1
0 3
2 5
4 7
6 8 10
9
Placebo
Metformin
Lifestyle
Years
10-YEAR INCIDENCE OF T2DM IN THE DPP
OUTCOMES STUDY

18. PHARMACOLOGIC INTERVENTIONS
PROVEN TO DELAY OR PREVENT
T2DM DEVELOPMENT
T2DM, type 2 diabetes mellitus.
Sherwin RS, et al. Diabetes Care.
2004;27,(Suppl 1): S47-S54.
Eriksson K-F, Lindgärde F.
Diabetologia. 1991;34:891-898.
Ramachandran A, et al. Diabetologia
2006;49:289-297.
Knowler WC, et al. N Engl J Med.
2002;346:393-403.
Defronzo RA, et al. N Engl J Med.
2011;364:1104-15.
Intervention
Rate of Conversion to Normal
Glucose Tolerance
Metformin (2 trials) 26%-31%
Acarbose (1 trial) 25%
Pioglitazone (1 trial) 48%

19. THE CHINESE PREVENTION STUDY
11.6
4.1
0
2
4
6
8
10
12
14
Incidence
of
Diabetes
(%/yr)
Control Metformin
The Effect of Metformin on the Progression
of IGT to Diabetes Mellitus (N=321)
IGT, impaired glucose tolerance; RRR, relative risk reduction.
Yang W, et al. Chin J Endocrinol Metab. 2001;17:131-136.
65%

20. EFFECT OF ACARBOSE ON
REVERSION OF IGT TO NGT
P<0.0001
Placebo Acarbose
Number
of
Patients
200
210
220
230
240
250
n=241
(35.3%)
n=212
(30.9%)
IGT, impaired glucose tolerance; NGT, normal glucose tolerance.
Chiasson JL, et al. Lancet. 2002;359:2072-2077.
The Study to Prevent Non-Insulin Dependent
Diabetes Mellitus (STOP-NIDDM)

21. PIOGLITAZONE FOR T2DM
PREVENTION IN IGT: ACT NOW
ACT NOW, Actos NOW for the Prevention of Diabetes;
IGT, impaired glucose tolerance; T2DM, type 2 diabetes mellitus.
Defronzo RA, et al. N Engl J Med. 2011;364:1104-1115.
Kaplan–Meier plot of hazard ratios for time to development of T2DM

22. OTHER ALTERNATIVE MEDICINE
• There's no definitive evidence that any alternative treatments are effective. Therapies that
have been said to be helpful and are also likely to be safe, include:
Cassia cinnamon
Flaxseed
Ginseng
Magnesium
Oats
Soy
Xanthan gum
www.mayoclinic.org/diseases-conditions/prediabetes/diagnosis-treatment/drc-20355284

23. TAKE HOME MESSAGES
• Prediabetes should not be viewed as a clinical entity in its own right but rather as
a risk factor for progression to diabetes and cardiovascular disease.
• The presence of prediabetes should prompt comprehensive screening for
cardiovascular risk factors.
• People with prediabetes have up to a 50% chance of developing diabetes over
the next five to 10 years. But steps can be taken to prevent Type 2 diabetes from
developing.