Yulianto

 Kusnadi  
 
Division  of  Endocrinology  and  Metabolism    
Department  of    Internal  Medicine,    Faculty  of  Medicine    
University  of  Sriwijaya/Mohammad  Hoesin  Hospital  Palembang  
History of Diabetes Mellitus

Diabetes Mellitus “Ebers Papyrus”

Greek for Latin for (Egyptian, 1500 B.C.)
“passing water
“sweetened first depiction of diabetes
like a siphon” with honey” mellitus
- urination of excess amounts
- manipulation of diet therapy
 3

The  diabetes  epidemic:  global  projecGons,  

2010–2030  
—  Adapted  from:  International  Diabetes  Federation.  IDF  Diabetes  Atlas,  5th  edn.  
Brussels,  Belgium:  International  Diabetes  Federation,  2011.  Available  at:    
http://www.idf.org/diabetesatlas  (accessed  April  2012).   World 2011 = 366 million
2030 = 552 million
Increase = 51%
52.8
37.7 64.2
51.2 22% 71.4
36% 120.9
69%

32.6
59.7
83%

131.9
25.1 187.9
14.7 42%
39.9
28.0
59%
90%
 0.0
2.0
4.0
6.0
8.0
10.0
12.0
Papua
NTB

1.7 1.8

Riskesdas, 2007
Bengkulu
Bali

3.03.0
Kalimantan  Tengah
Kepulauan  Riau
Sumatera  Selatan

3.2 3.3 3.4

Sulawesi  Barat
Sulawesi  Tenggara

3.7 3.8
Sumatera  Barat
NTT
Jawa  Barat
Sulawesi  Tengah 4.14.1 4.2
Sulawesi  Selatan
4.5 4.6

Maluku
4.8

Kalimantan  Selatan
Jambi
5.0 5.2

Sumatera  Utara
Banten
DI  Yogyakarta
5.35.3 5.4

Papua  Barat
Indonesia
5.5 5.7

Kalimantan  Timur
Lampung
6.0 6.2

DKI  Jakarta
Jawa  Timur
6.6 6.8

Gorontalo
Jawa  Tengah
7.7 7.8

Sulawesi  Utara
8.1

NAD
Bangka  Belitung
8.5 8.6
DM  Prevalence  by  Province  in  Indonesia  

Riau
10.4

Kalimantan  Barat
11.1

Maluku  Utara
11.1
The  progressive  nature  of  type  2  diabetes  leads  to  
loss  of  glycaemic  control  over  Gme1,2    
HbA1c levels often increase over time despite current treatment1

8
Median  HbA1c  (%)  

0 3 6 9 12 15
Time from randomisation (years)

Patients followed for 10 years All patients assigned to regimen

Conventional Conventional
Intensive Intensive

1. UKPDS Group. Lancet. 1998;352:837-53. 2. Kahn SE, et al. N Engl J Med. 2006;355:2427-43.
Normal Homeostasis
 Insulin
Resistance
Classification of Diabetes
Type 1 diabetes
β-cell destruction
Type 2 diabetes
Progressive insulin secretory defect
Gestational Diabetes Mellitus (GDM)
Other specific types of diabetes
Monogenic diabetes syndromes
Diseases of the exocrine pancreas, e.g., cystic fibrosis
Drug- or chemical-induced diabetes

American Diabetes Association Standards of Medical Care in Diabetes. 


Classification and diagnosis of diabetes. Diabetes Care 2017; 40 (Suppl. 1): S11-S24"
 10

Qualitative illustration of the spectrum of factors associated with different forms of DM,
including the variable age at onset, lack of obesity, metabolic syndrome, genetic associa-
tions, different forms of immune changes, C-peptide secretion, and the need for insulin
therapy. T1DM, type 1 DM; T2DM, type 2 diabetes
Pathogenesis of Type 2 Diabetes

An evolution theory:

- From triumvirate to ominous octet

(Ralph A. Defronzo)

- B-cell-centric construct: the egregious eleven

(Stanley S. Schwartz et.al)

11
Pathogenesis of type 2 diabetes: the triumvirate. Insulin resistance in muscle
and liver and impaired insulin secretion represent the core defects in type 2
diabetes 12
Pathogenesis of type 2 diabetes: the ominous octet
13
14
 15

Genetic determinants influence IR (whether centrally or peripherally

induced), loss of b-cell function and mass, environmental triggers (such as
viruses, endocrine disruptors, food advanced glycosylation end products,
gut biome), and immune modulation and inflammation.
 Risk factors for Prediabetes and T2DM

www.diabetes.org/are-you-at-risk

American Diabetes Association Standards of Medical Care in Diabetes. 


Classification and diagnosis of diabetes. Diabetes Care 2017; 40 (Suppl. 1): S11-S24"
 Criteria for the Diagnosis of Diabetes

Fasting plasma glucose (FPG)

≥126 mg/dL (7.0 mmol/L)
OR
2-h plasma glucose ≥200 mg/dL
(11.1 mmol/L) during an OGTT
OR
A1C ≥6.5%
OR
Classic diabetes symptoms + random plasma glucose
≥200 mg/dL (11.1 mmol/L)

American Diabetes Association Standards of Medical Care in Diabetes. 


Classification and diagnosis of diabetes. Diabetes Care 2017; 40 (Suppl. 1): S11-S24"
What  is  prediabetes?  
—  Blood  sugar  is  higher  than  normal  but  not  as  high  as  
diabetes  
—  Touch  of  sugar  
—  Mild  diabetes  
—  Impaired  Fasting  Glucose  (IFG)  and/or  Impaired  
Glucose  Tolerance  (IGT)  
 Prediabetes

FPG 100–125 mg/dL

(5.6–6.9 mmol/L): IFG
OR

2-h plasma glucose 140–199 mg/dL (7.8–11.0 mmol/L): IGT

OR

A1C 5.7–6.4%

American Diabetes Association Standards of Medical Care in Diabetes. 


Classification and diagnosis of diabetes. Diabetes Care 2017; 40 (Suppl. 1): S11-S24"
THE  GLUCOSE  TRIAD  
Achieving  op,mal  control  of  HbA1c  requires  daily  
control  of  PPG  and  FPG  –  the  glucose  triad1-­‐3    
Both postprandial and fasting glucose contribute to HbA1c levels1-3

HbA1c = PPG + FPG

Influenced by: Influenced by:

•  Pre-prandial glucose
•  Glucose load from meal
•  Incretin level
•  Insulin secretion
•  Insulin sensitivity in
peripheral tissues
•  Decrease in glucagon
suppression
•  Hepatic glucose production
•  Hepatic sensitivity to insulin
•  Exercise during previous day
•  Meal from the previous night
•  Alcohol
•  Nocturnal glycaemia

1. IDF. International Diabetes Foundation. Guidelines for Postmeal Glucose. Available at:
http://www.idf.org/webdata/docs/Guideline_PMG_final.pdf. Accessed 26 Jan 2009. 2. Monnier L, et al. Diabetes Metab. 2006;32:2S11-16. 3. Woo V, et al.
Int J Clin Pract. 2008;62:1935-42.
Antihyperglycemic therapy: general recommendation (ADA 2017)
Treatment of type 2 diabetes: a therapeutic approach
based upon pathophysiology.
24
Prevention or Delay
of Type 2 Diabetes
 RecommendaGons:  PrevenGon  or  Delay  of  T2DM  
—  Patients  with  prediabetes  should  be  referred  to  an  
intensive  diet  and  physical  activity  behavioral  counseling  
program  adhering  to  the  tenets  of  the  DPP  targeting  a  loss  
of  7%  of  body  weight,  and  should  increase  their  moderate  
physical  activity  to  at  least  150  min/week.  A  

American Diabetes Association Standards of Medical Care in Diabetes. 


Prevention or delay of type 2 diabetes. Diabetes Care 2017; 40 (Suppl. 1): S44-S47"
 RecommendaGons:  PrevenGon  or  Delay  of  
T2DM  (2)  

—  Metformin  therapy  for  prevention  of  type  2  diabetes  

should  be  considered  in  those  with  prediabetes,  especially  
for  those  with  BMI  >35  kg/m2,  aged  <  60  years,  women  
with  prior  gestational  diabetes  (GDM),  those  with  rising  
A1C  despite  lifestyle  intervention.  A  

American Diabetes Association Standards of Medical Care in Diabetes. 


Prevention or delay of type 2 diabetes. Diabetes Care 2017; 40 (Suppl. 1): S44-S47"
Glycemic Control and
Targets
 Assessment  of  Glycemic  Control  
—  Two  primary  techniques  available  for  health  providers  and  
patients  to  assess  effectiveness  of  management  plan  on  
glycemic  control  
1.  Patient  self-­‐monitoring  of  blood  glucose  (SMBG)  
2.  A1C  
—  CGM  or  interstitial  glucose  may  have  an  important  role  
assessing  the  effectiveness  and  safety  of  treatment  in  
selected  patients.  

American Diabetes Association Standards of Medical Care in Diabetes. 


Glycemic targets. Diabetes Care 2017; 40 (Suppl. 1): S48-S56"
 Glycemic  RecommendaGons  for  Nonpregnant    
Adults  with  Diabetes    

A1C" <7.0%* 

" (<53 mmol/mol)"
Preprandial capillary 
 80–130 mg/dL* 

plasma glucose" (4.4–7.2 mmol/L)"
Peak postprandial <180 mg/dL* 

capillary plasma glucose†" (<10.0 mmol/L)"

* Goals should be individualized."

† Postprandial glucose measurements should be made 1–2 hours after
the beginning of the meal."
American Diabetes Association Standards of Medical Care in Diabetes. 

Glycemic targets. Diabetes Care 2017; 40 (Suppl. 1): S48-S56"
 Individualized Treatment based on
several criteria to control blood glucose

Inzucci SE, et al. Diabetologia. Slide

201231
Diabetes  complicaGons  
—  Acute  
 -­‐  Diabetic  ketoacidosis  (DKA)  
 -­‐  Hyperosmolarity  Hyperglycemia  State  (HHS)  
 -­‐  Hypoglycemia  
 
—  Chronic  
-­‐  Macroangiopathy  
-­‐  Microangiopathy  
-­‐  Neuropathy  
 General Features of Hyperglycemia-
Induced Tissue Damage
Genetic determinants
of individual
susceptibility

Repeated acute
changes in
cellular
metabolism
Diabetic tissue
Hyperglycemia damage
Cumulative long-
term changes
in stable
macromolecules

Independent
accelerating factors
(e.g. hypertension,
dyslipidemia)

DIABETES, VOL. 54, JUNE 2005

 Possible Pathogenesis of Diabetic
Complications"

Overall Glycemic Control (HbA1c)

Hyperglycemic Fasting/Preprandial
" "Peaks"" glucose elevations"

"

Acute toxicity Chronic toxicity"

Tissue lesion

Complications
Macrovascular  complicaGons  

—  Coronary  heart  disease  

—  Cerebrovascular  disease  
—  Peripheral  vascular  disease  
 
 
Diabetic  patients  have  a  2  to  6  times  higher  risk  for  
development  of  these  complications  than  the  
general  population  
Eye Complications
Retinopathy (stages)
Background
Pre-proliferative
Proliferative
Advanced diabetic eye disease
Maculopathy
Glaucoma
 Diabetic Nephropathy Evolves to End Stage
Renal Disease Through Several Stages

Levey AS et al, Kidney Int 13 June 2007;doi:10,1038/sj.ki.5002343

Lessons from UKPDS:
Better control means fewer complications

EVERY 1% REDUCED RISK*

reduction in HBA1C

Deaths from diabetes -21%

Heart attacks -14%

1% Microvascular complications -37%

Peripheral vascular disorders -43%

UKPDS 35. BMJ 2000; 321: 405-12 *p<0.0001