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Ueda2016 do we know what is type 2 -assem zeyada
1. Dr. Assem A. Zeyada M.D.
Emeritus Professor of Internal
Medicine
Consultant of Endocrinology
Cairo University & Hospitals
Do We Know What Is
Type 2 Diabetes?
3. Joslin 1916
we need standards for diagnosis of diabetes
Fajans 1978
Diabetes should be considered as a heterogeneous
group of disorders affecting carbohydrate protein
and fat metabolism due to relative or absolute
insulin deficiency with specific microvascular
complications and high incidence of macrovascular
complications
ADA 1997
A group of metabolic disorders characterized by
hyperglycemia due to defects in insulin secretion
and or action with consequent long term damage,
dysfunction and failure of various organs
4. Type 2 Diabetes
2015
Where are we?
The Plague of the century
The Global burden for governments
economy worldwide
The Ghost we are fighting
5. Incidence and prevalence are increasing
tremendously worldwide
Previously a disease of adults, is creeping to
adolescent and late childhood (linked to pubertal
growth)
The Plague Of The Century
6. Insidious onset with transition from prediabetes to
diabetes within years according to prediabetes definition
20-30% of prediabetics in the stage of IFG or/and
IGT suffer microvascular, neuropathic and macrovascular
complications
Diabetes commonly remains asymptomatic for variable
period (usually few years). Diagnosis may be made under
the following conditions:
The Ghost we are fighting
When Symptoms become florid Or
Occurrence of diabetes-specific complications Or
Different settings of clinical scenarios Or
Routine check up
Selective population-based screening is cost effective but is
not feasible
9. Despite Herculean efforts, single nucleotide
polymorphisms (Diabeto SNPs)exceed 30 and most are
unknown . Many ethnic groups are not yet studied
In conclusion: Robust Genetic Prediction and personalized
Diabetes Intervention remains a distant hope
With time many deleterious factors are identified which
empower the continuity of the plague
Long Term Exposure to traffic related air pollution in
healthy physically active and non smokers; contributes to
the development of Diabetes
Anderson Z, J Raachou-Nielsen O et al
Diabetes Care 2012;35:92-98
Genetic Basis
DAGOGO-JACK S.Commentary
Diabetes Care 2012;35:193-195
Environmental Hazards: beside unhealthy life style
12. Islet Dysharmony
Islet paracrinopathy:
sensitivity of α-cell to
endogenous insulin
hyperglucagonemia
Many yet unknown
During the show many come into the play e.g
hypertension, Dyslipidemia, mitochondrial
dysfunction, oxidative stress and amyloid
Islets in Type 2 DM
β - Cell mass
Programmed in
utero
Apoptosis exceeds
neogenesis
Islets derived
cytokines
β - Cell defect
programmed in
utero
- AIR
- Lost 1st phase
insulin secretion
- Diabetes
13. Acute Insulin Response Vs Proinsulin Level
Cumulative incidence of DM: Prospective study for 27 years over
children with +ve FH of Type 2
AIR
(pmol/L)
Proinsulin
(pmol/L)
T1 < 282
T2 282 – 456
T3 > 456
< 1.7
1.7 - 3.1
> 3.1
Zethelius B. et al Diabetetologia 2003; 46 : 20 - 26
15. Starts many years before the onset of abnormal glucose
tolerance possibly traced to genetic and embryonic
programming
Beside poorly understood mechanisms, the primacy and
supremacy of skeletal muscle, liver and adipose tissue remains
extremely controversial
Anywhere insulin resistance starts, the resulting
hyperinsulinemia and finally hyperglycemia induce insulin
resistance in all insulin-sensitive tissues and perpetuation
continues
Chronic inflammatory process is a common associate and
augment the whole cascade
17. Healthy diet and calorie restriction aiming at B.wt
reduction especially in obese
Increased physical activity. Beside helping body weight
reduction is beneficial regarding depression and dyslipidemia
Self Management Diabetes Education (SMDE)
considered now the gold standard , but handicaps are
many with increasing life stresses
Pharmacotheray
The ideal drug(s) is still unknown. Metformin remains the
best and the denominator for all drug combinations
Bariatric Surgery
When indicated for the proper patient , proved effective in
improving diabetes and other CVRs
In Management
Life Style Modification
18. Extra pancreatic
Type 2 D.M
Where are we ?
Pancreatic
A circus initiated by
localised autoimmune
process and induced
by epitopes from
apoptotic B-cells
Determined genetically
and by intrauterine
environment
Hypothalamic Incretin Defect
Imbalance between Unidentified
Orexigenic and defect(s) in
Anorexigenic GIP-1 system
centres
19. Type 2 diabetes is a state of hyperglycemia emanating from
islet dysfunction and insulin resistance which occur early in life
and progress steadily. The mechanisms behind both are poorly
understood
Alternatively it may represent a component of dysmetabolic
syndrome again of unknown nature
For the moment no ideal therapeutic approach exists and
chronic complications continue
Still gloomy. We are facing an epidemic with enormous human
suffering and economic costs
Lessons from UKPDs, Accord, ADVANCE, VDAT and others
advocate early intervention at the onset or even before
hyperglycemia and aggressive treatment in the young
especially with increasing body weight
Conclusion