Diabetes Mellitus

Dharma Lindarto

Div. Endokrin-Metabolik. Departemen Ilmu Penyakit

Dalam FK USU / RSUP H Adam Malik Medan
 Definition

Diabetes Mellitus is a heterogeneous

group of conditions characterized by
hyperglycaemia
 Prevalence of diabetes

 1 million Type
Type 1 GDM
1
6% 1%

Type 2 undx
 11 million Type
2 diagnosed
33%

 6 million Type
Type 2, dx
60%

2 undiagnosed

 150,000 GDM
Prevalence of diabetes type 2
6.2 % of total population
20% of persons over 65
Highest in certain ethnic groups
– African American (up to 12%)
– Asian American (up to 22%)
– Latin American (up to 20%)
– Native American (up to 60%)
 Incidence of diabetes type 2

 800,000 new cases every year

 2,000 new cases every day

 Etiological Classification of Diabetes Mellitus

I. Type 1 diabetes* - previously known as

juvenile diabetes
insulin-dependent diabetes mellitus (IDDM)
II. Type 2 diabetes* - previously known as
adult-onset diabetes
non-insulin-dependent diabetes mellitus (NIDDM)
III. Other specific types (includes Secondary Diabetes)
IV. Gestational diabetes mellitus (GDM)

*Patients with any form of diabetes may require insulin

treatment at some stage of their disease. Such use of insulin
does not, of itself, classify the patient.

American Diabetes Association: Clinical Practice Recommendations,

updated annually and published as a supplement to Diabetes Care and at
http://care.diabetesjournals.org/
 Type 1 diabetes mellitus
T cell-mediated destruction of pancreatic ß-cells
Rapid onset, usually in childhood
Complete insulin deficiency
Absolute insulin requirement
 1,000,000 cases in U.S.
 Natural History of Type 1
Diabetes Mellitus

b Cell Mass
Ab+ve

Antibody Negative (Ab-ve)

ABN
GTT

Fasting Blood Sugar

Type 2 Diabetes is characterized by
Hyperglycaemia and

•Insulin Resistance
•Impairment in insulin secretion
Insulin Resistance
 Type 2 diabetes mellitus
Ranges from predominantly insulin resistance with
relative insulin deficiency to a predominantly
secretory defect with insulin resistance
Insulin required in 20-30% of patients
Heterogeneous polygenic disease
Progression gradual
Influenced by environmental factors
20
15,000,000 cases # patients,
in millions
in the U.S. 15

18% of the population 10

 65 years old 5

0
total type 1 type 2
 Gestational diabetes mellitus
(GDM)
Any degree of glucose intolerance with onset
during pregnancy
Return to normal glucose regulation after delivery
is common
Increased perinatal morbidity and mortality if
untreated
 Other specific types of DM
A. Genetic defects of ß-cell function
B. Genetic defects in insulin action
C. Diseases of the exocrine pancreas
D. Endocrinopathies
E. Drug- or chemical-induced
F. Infections
G. Uncommon forms of immune-mediated diabetes
H. Other syndromes sometimes associated with
diabetes
 Pathophysiology Type 2 DM
Genes
Obesity
Sedentary Lifestyle
Aging
 The progressive nature of insulin resistance

Insulin resistance

Hyperinsulinaemia

Increasing insulin resistance Impaired glucose tolerance

b-cell failure Hyperglycaemia/

Type 2 diabetes

Hypoinsulinaemia
Arner, EASD (1999)
 Pathology of Type 2 diabetes
Lack of exercise/
high-fat diet
Insulin resistance
Central obesity

Genetic factors Insulin secretion Blood glucose

Insulin secretion
Poor pancreatic
development b-cell function
 Pathology of Type 2 diabetes
• Peripheral resistance to insulin and/or a deficiency of
insulin secretion resulting in:
– hyperglycaemia
– hyperinsulinaemia
– premature exhaustion of b-cells
• As part of this complex metabolic disorder a number
of factors are frequently compromised:
– carbohydrate metabolism
– lipid metabolism
– protein metabolism
• Disease progression is often insidious and occurs over
many years
Symptoms
Polyuria
Polydipsia/nocturia
Tiredness
Weight loss (Type 1)
Blurred vision
Ketones in urine (Type 1)
Dehydration
 ADA Clinical Practice Recommendations
Diagnosis of Diabetes
• HbA1c  6.5%
– Test performed NGSP certified and standardized to DCCT
• FPG  126 mg/dl
– No caloric intake for at least 8 hours
• 2 hour glucose  200 mg/dl during an OGTT
– Test performed as per WHO (75 g glucose)
• If classic symptoms of hyperglycemia = random glucose  200
mg/dl

NORMAL PREDIABETES IFG or IGT DIABETES

FPG < 100 FPG > 100 – 125 (IFG) FPG > 126

2-h PG < 140 2-h PG 140 – 199 (IGT) 2-h PG > 200

HbA1c < 5.7% HbA1c 5.7 – 6.4%H HbA1c > 6.5%

American Diabetes Association. Diabetes Care 323(Suppl 1), 2009
Confirming the Diagnosis with Repeat Testing

If one test (HbA1c, FPG, OGTT) is positive and one test is

negative for the diagnosis of diabetes
• Repeat the positive test
If the 3rd test is positive = DM
If the 3rd test is negative, follow closely (repeat in approx. 6 months,
counsel in lifestyle management)
Ex – HbA1c 6.7%, FPG 121 mg/dL – repeat HbA1c
• 3rd test HbA1c is 6.6% = diabetes
• 3rd test HbA1c is 6.3% - follow closely, lifestyle counseling
Ex - A1c 6.6% repeat HbA1c 6.3% – repeat HbA1c
• 3rd test HbA1c is 6.7% = diabetes
• 3rd test HbA1c is 6.2% - follow closely, lifestyle counseling
 Complications of Diabetes
Stroke

Blindness: retinopathy,
glaucoma, cataracts

Coronary heart disease

Renal failure
Infections

Autonomic neuropathy

Peripheral neuropathy

Peripheral vascular disease

Amputations
 Oral Disease and Systemic Disorders

Periodontitis has an association with:

• Infective Endocarditis
• Diabetes
• Cardiovascular Disease
• Pre-Term, Low Birth Weight Infants
• Pulmonary Disease
• Others
Epidemiologic Studies in the Pimas:
Shlossman, Emrich, Knowler, Nelson and others

 Diabetics had more severe periodontitis than

non-diabetics.
 Destructive periodontitis occurred much earlier
in life in the diabetics (27% of diabetics 15-19
years old).
 Diabetics were 15X more likely to lose all their
teeth.
 Diabetes and Periodontitis
A recent review of 55 studies involving subjects with
diabetes found consistent evidence of greater
periodontitis:
•Prevalence
•Incidence
•Severity
•Extent
•Progression

Dose-response relationship- as glycemic control

worsens, periodontitis worsens.
Taylor, CCED 2004
Periodontal destruction associated with diabetes

PMN’s-chemocytosis
phagocytosis
High glucose
Glycation AGE
Abnormal lipids
RAGE
Sorbitol
Hyper-responsive
monocytes;
 IL-1, IL-6, & TNF- α endothelial cells
 collagenase
 O2 free radicals

Susceptibility to severe periodontitis

 DM and Periodontitis- The 2 Way Relationship
DM
 serum lipids AGE binding/accumulation
 blood glucose
Inflammatory State
Destructive Environment

Further aggravated lipid

metabolism &  insulin Periodontal
Pathogens
resistance
Increased
Periodontitis, with Periodontal
additional  PgE2 Destruction
& cytokines IL-
1ß, IL-6, & TNF-
α
Review
Severe Periodontal Disease
 Recommendations
Regular dental examinations for all DM
patients
Aggressive periodontal therapy for
infections
Frequent reinforcement of oral hygiene
and dental care by medical providers
 DM: Goals of Therapy

 Decrease morbidity and mortality

 CHD, Stroke

 Maximize therapy of CV risk factors

 Identify and treat complications early

 Maintain function/quality of life

 Minimize side effects

 Prevention of
Complications

 Coronary heart disease

 Stroke
 Ischemic peripheral vascular disease
 Retinopathy
 Nephropathy
 Neuropathy
Coronary Heart Disease and
Stroke

 Smoking cessation

 Daily aspirin therapy

 Hypertension control

 ACE inhibitors, ß-blockers,

Diuretics

 Treatment of dyslipidemia
evention of Microvascular Complications

 Control of blood pressure

 Glucose control

 Early identification and treatment of

neuropathy, nephropathy, and
retinopathy
 Treatment of Type 2 Diabetes
Diet and exercise
–80 % of Type 2 diabetics are obese
–  caloric intake
 physical exercise }  insulin sensitivity

–first line of treatment

–recent clinical trial showed that exercising at least
30 minutes a day reduces Type 2 risk more
effectively than medication
 Treatment of Type 2 Diabetes
•Monotherapy with oral agent
•Combination therapy with oral agents
•Insulin +/- oral agent
–insulin required in 20-30% of patients

With duration of the disease, more intensive

therapy is required to maintain glycemic goals
 Insulin Preparations

Peak Duration
Preparation Onset (hrs) (hrs)
Lispro (rapid- 10 - 30
acting) mins 0.5 - 1 3-5
Regular (short- 30 – 60
acting) mins 1.5 – 2 5 - 12
Premixed 30 – 60
(70% NPH/30% R) mins 3 (2-12) 13 - 18
NPH/Lente
(intermediate-
acting) 1-2 hrs 4 -8 10 - 20
Ultralente (long-
acting) 2 – 4 hrs 8 - 20 16 - 24
Glargine (long-
acting) 1 – 2 hrs No peak 24 hours
Oral Drugs in Type 2 DM
Sulphonylureas
Biguanides
Alpha glucosidase inhibitors
Meglitides
Thiazolidediones
DPP-4 Inhibitor
SGLT-2