1. Type 2 Diabetes in Youth
By: W.L Benjamin
14th November 2015

2. Diabetes Mellitus
Is a group of metabolic diseases characterised by hyperglycaemia resulting from defects in insulin secretion, insulin action or both.

4. How is the diagnosis made?
Simple inexpensive blood test, the serum blood glucose level.
Diagnostic criteria consists of:
Symptoms of diabetes + a random blood glucose of >11 mmmol/l or
Fasting blood glucose of >7mmol/l or
A glucose level of >11mmol/l, 2hrs after a 75g glucose load (GTT)

5. Criteria Continues:
Glucose level mmol/l= impared glucose Tolerance (ITG)
Controversy ???fasting glucose ?6.1 or ?5.6mmol/l
The reading between normal fasting glucose (NFG) and diagnostic level (7mmol/l)=Impared fasting glucose

6. Impared fasting glucose vs Impared glucose Tolerance
IFG alone is primary marker of low insulin levels (plus insulin resistance).
Patients are at increased risk of CAD, but less than patients with IGT.
Also at increased risk of developing diabetes but less than patients with IGT.
IGT patients have increased risk of CAD, and higher risk of developing diabetes than those with IFG.

7. IFG VS IGT
Patients with both IFG and IGT have the highest risk for CAD and of developing diabetes.

8. What is the Role of HbA1c?
HbA1c .6.5% can be considered diagnostic of diabetes.
5.7%-6.4% “category of increased risk of future diabetes
NB: HbA1c test alone has been rejected by most medical aids in SA and Namibia.

9. What Do We Know About Type 2 Diabetes in Youth?
Question
What Do We Know About Type 2 Diabetes in Youth?

10. Is it an epidemic?
The incidence is increasing and probably underestimated
Population based estimates indicate an ~10-fold increase in incident cases over the past years
8% to 43% of all new cases of diabetes
The SEARCH Trial
What about prevalence??
Bloomgarden ZT. Diabetes Care. 2004;27: Centers for Disease Control. Diabetes Fact Sheet. 2005

11. Question Is the Presentation the Same as in Adults?
Does not appear to be preceded by long asymptomatic period
Do not find undiagnosed cases on screening

12. Natural History of Type 2 Diabetes
Complications
Genetic susceptibility
Environmental factors
Onset of diabetes
Disability
P R E
Obesity Insulin resistance
Ongoing hyperglycemia
Death
Risk for
Disease
Metabolic
Syndrome
Blindness Renal failure CHD Amputation
Atherosclerosis Hyperglycemia Hypertension
Retinopathy Nephropathy Neuropathy

13. Pre-diabetes (IGT) and T2D
Overweight Sample
IGT
T2D
Paulsen et al, 1968
66 multi-ethnic youth (4- 16 years)
17% 6%
Weninger et al, 1980
15 subjects
33% 0%
Sinha et al, 2002
55 multi-ethnic youth (>95th %ile)
25%
112 multi-ethnic teens (>95th %ile)
21% 4%
Goran et al, 2004
150 Hispanic +FH
(8-13 years >85th %ile)
28%
IGT = Impaired Glucose Tolerance

14. Type 2 Diabetes ? Curve for Youth B-cell Function (%)
Progressive Pancreatic B-cell Failure
Prevention and Early Treatment
UKPDS Data
B-cell Function (%)
? Curve for Youth
Years from Clinical Diagnosis

15. Occurs at the time of intense insulin resistance due to puberty
Question
Is the Pathophysiology the Same as in Adults?
Associated with significant ß-cell failure as well as insulin resistance
Occurs at the time of intense insulin resistance due to puberty

16. Polycystic ovary syndrome
Type 2 Diabetes
Prediabetes
Beta Cell Defect
Beta Cell Defect
Age
Puberty
Obesity
BP,
Lipids
Insulin Resistance
Genetics
Ethnicity
Sedentary Lifestyle
Gender – Girls
Polycystic ovary syndrome

17. Insulin Resistance Beta Cell Defect Type 2 Diabetes Prediabetes
Autoimmunity
Genetic Defect
Beta Cell Defect
Fat cell
toxicity
Intrauterine
IUGR, DM
Glucose
toxicity
Insulin Resistance

18. What distinguishes type 1 from type 2 diabetes in youth?
Question
What distinguishes type 1 from type 2 diabetes in youth?

19. Type 1 Versus type 2 Diabetes in youth?
T1DM
T2DM
Weight
20% may be overweight / obese
Virtually all BMI > 85%th percentile
Course
Rapid
From DPT-1 can be indolent
Indolent
Virtually none found on screening
DKA
35%-40%
Ketonuria (33%)
Mild DKA (5%-25%)
Relative with DM
5% with T1DM
Up to 30% may have with T2DM
FH of T2 2-3Xs in person with T1
74%-100% - 1st –2nd degree with T2DM
Comorbid
Thyroid, adrenal, vitiligo, celiac
Increase in polycystic ovary syndrome
Acanthosis nigricans
C-peptide
C-peptide can be preserved at DX
Normal or increased
Antibody
Ethnicity
85%
Whites predominate
15% (reported as high as 30%)
NA, AA, HA, Asian, Pacific Islander
Kaufman,Endocrinol Meta Clinics N Am, 34; : 2005

20. Differentiation Between Type 1 and 2
48 with type 2 vs 39 with type 1
Type 2
Ethnicity, 1st degree relative, BMI>24, +C- peptide, acanthosis
Type 2
Type 1
DKA
33%
53%
C-peptide
ug/l
ug/l
Abs
8.1% ICA
30% GAD 35%IAA
85% have islet autoimmunity
Hathout et al Pediatrics 107e102,June,2001

21. Question How Does Type 2 Present in Youth?
Is it asymptomatic or symptomatic in youth?

22. Diagnosis with Type 2 Fagot-Campagna et al J Pediatr 2000
Mean Age years
Girls > Boys :1
Obese BMI >85th %
Minority Groups 94%
Strong Family History %
Acanthosis Nigricans %
Diagnosis made by Symptoms, not Screening
HbA1c %
Weight loss %
Glucose in urine 95%
Ketosis %
DKA %

23. Question What Are Treatment Targets in Youth with Type 2 Diabetes?
Are they the same as in adults?

24. TREATMENT GOALS Glucose control, HbA1c <7%
Goals (Diabetes Care, 2000) FG PP
Bed
A1c <7.0
TREATMENT GOALS
Glucose control, HbA1c <7%
Eliminate symptoms of hyperglycemia
Maintenance of reasonable body weight
Improve cardiovascular risk factors
Reduce microvascular complications
Improvement in physical and emotional well-being

25. Start with insulin and diet, exercise
Diagnosis
BG 250 mg/dL or 12 mmol/L
Asymptomatic
Start with insulin and diet, exercise
Diet and exercise
<7%
<7%
Monthly review, A1C q3mo
Add metformin
Attempt to
wean insulin
>7%
Add metformin
>7%
Add insulin, TZD, sulfonylurea
>7%
Add 3rd agent
TZD = thiazolidinedione
Silverstein JH, Rosenbloom AL.
J Pediatr Endcrinol Metab. 2000;13 Suppl 6:

26. T1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus.
Intensive Therapy for Diabetes: Reduction in Incidence of Complications
T1DM
DCCT
T2DM
Kumamoto
UKPDS
A1C
9%  7%
8%  7%
Retinopathy
63%
69%
17%–21%
Nephropathy
54%
70%
24%–33%
Neuropathy
60%
58% –
Cardiovascular disease
41%*
52*
16%*
Review Data
T1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus.
*Not statistically significant due to small number of events.
†Showed statistical significance in subsequent epidemiologic analysis.
DCCT Research Group. N Engl J Med. 1993;329: ; Ohkubo Y, et al. Diabetes Res Clin Pract. 1995;28: ; UKPDS 33: Lancet. 1998;352: ; Stratton IM, et al. Brit Med J. 2000;321:

27. Uncontrolled diabetes
Amputations
Loss of Sensations
Heart disease
and strokes
Blindness
Uncontrolled diabetes
can lead to…
Death
Kidney failure

28. STOPP-T2 TREATMENT PRIMARY AIM
To compare the efficacy of 3 treatment regimens
Metformin
Metformin + lifestyle
Metformin + TZD
On Time to Treatment Failure and on Glycemic Control
TODAY

29. Primary Outcomes Treatment goal Treatment failure
HbA1c < 6% (glycemic control)
Treatment failure
HbA1c  8.0% over 6 consecutive months OR
Inability to wean from temporary insulin therapy due to metabolic decompensation

30. Outcome Measures Glycemia Insulin sensitivity and secretion
HbA1c, fasting and postprandial glucose by home monitoring
Insulin sensitivity and secretion
OGTT, HOMA, QUICKI, proinsulin, C-peptide
Body composition
BMI, DEXA, waist circumference, abdominal height
Fitness and physical activity
PDPAR, PWC 170, accelerometer

31. Outcome Measures (continued)
Nutrition
food frequency questionnaire
Cardiovascular disease risk
BP, lipids, inflammatory markers, coagulation factors
Microvascular complications
microalbuminuria, neuropathy
Quality of life
Cost

32. National Diabetes Education Program’s Tip Sheets for Kids with Type 2
                        
In terms of publications, these colorful tip sheets provide basic information about type 2 diabetes and encourage young people to take steps to manage the disease for a long and healthy life.
Written in simple language, the tip sheets are helpful for anyone who has type 2 diabetes and their loved ones. Topics include:
What is Diabetes?
Be Active.
Stay at a Healthy Weight.
Eat Healthy Foods.
These tip sheets also are available online on the NDEP website.
Additional tip sheets are in development covering dealing with diabetes and diabetes prevention.
What is Diabetes?
Be Active
Stay at a Healthy Weight
Eat Healthy Foods

33. Conclusion Increased incidence Difficult to distinguish from type 1
Occurs at the time of intense insulin resistance due to puberty
Does not appear to be preceded by long asymptomatic period
More insulin deficiency and requirement for exogenous insulin early
Safety and efficacy of therapeutic agents
Rapid progression of co-morbidities and complications

34. Thank you Q & A