Diabetes Mellitus
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Global and national prevalence of diabetes
Types of diabetes
Pathogenesis of diabetes
Classification and criteria for lab diagnosis of diabetes
Lab investigations for a patient of diabetes
MCQ’s
The Miracle of Insulin
Patient J.L., December 15, 1922
February 15, 1923
Diabetes Mellitus
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“Diabetes is a dreadful affliction,---------”.
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Areteus of Cappadosia in 2nd Century.
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It continues to be a sinister disease, if not taken care
of.
Sheikh M.Z, Diabetes Mellitus: The Continuing Challenge,
JCPSP 2004 Vol.14(2), 63-64
Diabetes a global epidemic
Years
Diabetics
(Million)
1998
135
2003
170
2025
300
Sheikh M.Z, Diabetes Mellitus: The Continuing Challenge,
JCPSP 2004 Vol.14(2), 63-64
WHO Estimates
WHO ranks Pakistan 7th on diabetes
prevalance list-
(The Nation ; English Daily- 15th
Nov 2008)
Pakistan ranked
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eighth in the world for Diabetes Mellitus (1995),
After India, China, USA, Russia, Japan, Brazil, and Indonesia.Asian
and
other developing countries have higher prevalence of
diabetes mellitus as compared to Western population
Sheikh M.Z, Diabetes Mellitus: The Continuing Challenge,
JCPSP Vol.14(2) 63-64 ,
Diabetes epidemiology in Pakistan
Years
Diabetics
(Million)
1995
4.3
2025
14.5
Sheikh M.Z, Diabetes Mellitus: The Continuing Challenge,
JCPSP 2004 Vol.14(2) 63-64
The provincial prevalence of
diabetes mellitus- Pakistan
Province
Diabetes
Balochistan
8.4%
Kyber Pakhtun Khwa
(KPK)
11.1%
Sindh
13.9%
Punjab*
10.9
Basit .A et al, Frequency of Chronic Complications of type II Diabetes
JCPSP 2004 Vol.14 (2): 79-83
*Shera AS et a; Pak national diabetes survey, J of Primary Care Diab, 2010 Vol 4 79-83
Gender prevalence of DM
Diabetes Mellitus
Males
16.2%
Females
11.7%
Impaired Glucose Tolerance
Males
8.2%
Females
14.3%
Sheikh M.Z, Diabetes Mellitus: The Continuing Challenge,
JCPSP 2004 Vol.14(2) 63-64
SURGE IN DIABETES MELLITUS
 Developing
countries > 200%
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Developed countries > 45%
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Type 2 diabetes, will be 90% of all cases.
Sheikh M.Z, Diabetes Mellitus: The Continuing Challenge,
JCPSP 2004 Vol.14(2) 63-64
Normal Pancreatic Islets:
ß cells
Glucagon cells
Insulin Promotes Anabolism
Insulin lowers plasma glucose by:
1. Increasing glucose transport into
most insulin sensitive cells
2. Enhancing cellular utilization and
storage of glucose
3. Enhancing utilization of amino
acids
4. Promoting fat synthesis
INSULIN
Glucagon Is Dominant In The Fasting State
Glucagon prevents hypoglycemia.
Glucagon is secreted when plasma glucose
levels fall below 100 mg/dL.
The liver is the primary target of glucagon.
Glucagon stimulates glycogenolysis and
gluconeogenesis to increase glucose output
by the liver.
Glucagon release is also stimulated by
plasma amino acids.
GLUCAGON
Pathogenesis of Type 1DM
Genetic
HLA-DR3/DR4
Environment ?
Viral infe..??
Autoimmune Insulinitis
ß cell Destruction
Severe Insulin deficiency
Type 1 DM
Natural History Of “Pre”–Type 1 Diabetes
-Cell
mass 100%
Putative
trigger
Cellular autoimmunity
Circulating autoantibodies (ICA, GAD65)
Loss of first-phase
insulin response (IVGTT)
Clinical
onset—
only
Glucose intolerance
10% of
(OGTT)
-cells
remain
Genetic
predisposition
Insulitis
-Cell injury
“Pre”diabetes
Diabetes
Time
Eisenbarth GS. N Engl J Med. 1986;314:1360-1368
14
Insulinitis
Type 1 DM
Pathogenesis of Type 2 DM
Environment
Obesity ???
ß cell defect
Genetic
Abnormal Secretion
Insulin resistance
Relative Insulin Def.
ß cell
exhaustion
Type 2 DM
IDDM
Is It Gluttony or Sloth??
Jack in the Box
Average American
Bacon Ultimate Cheeseburger
child or teen
1020 Calories
watches 3-4 hours TV
per day
71 grams of Fat
H4046
Subcutaneous Fat
Gluteal Fat
Viceral Fat
Islets in Type 2 Diabetes:
Loss of ß cells
Amyloid deposits
Hyalinization
Natural History of Type 2 Diabetes
Impaired
glucose tolerance
Undiagnosed
Known diabetes
diabetes
Insulin resistance
Insulin secretion
Postprandial glucose
Fasting glucose
Microvascular complications
Macrovascular complications
Adapted from Ramlo-Halsted BA, Edelman SV. Prim Care. 1999;26:771-789
17
Type-1
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Age: < 40 Years
Duration: Weeks
Ketonuria: Common
Insulin- Dependent
Autoantibody: Yes
Family History: No
Insulin levels: very low
Islets: Insulinitis
Complications:
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Acute & Metabolic
Type-2
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> 40 Years
Months to years
Rare
Independent *
No
Yes
Normal or high *
Normal / Exhaustion
Complications
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Late and vascular.
I. CLASSIFICATION AND
DIAGNOSIS OF DIABETES
Classification of Diabetes
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Type 1 diabetes
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Type 2 diabetes
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β-cell destruction
Progressive insulin secreting defect
Other specific types of diabetes
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Genetic defects in β-cell function, insulin action
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Diseases of the exocrine pancreas
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Drug- or chemical-induced
Gestational diabetes mellitus
ADA. I. Classification and Diagnosis. Diabetes Care 2011;34(suppl 1):S12.
Criteria for the Diagnosis of Diabetes
HbA1C ≥6.5%
OR
Fasting plasma glucose (FPG)
≥126 mg/dl (7.0 mmol/l)
OR
Two-hour plasma glucose ≥200 mg/dl (11.1 mmol/l)
during an OGTT
OR
A random plasma glucose ≥200 mg/dl (11.1 mmol/l)
ADA. I. Classification and Diagnosis. Diabetes Care 2011;34(suppl 1):S13. Table 2.
Prediabetes: IFG, IGT, Increased A1C
Categories of increased risk for diabetes (Prediabetes)*
FPG 100-125 mg/dl (5.6-6.9 mmol/l): IFG
or
2-h plasma glucose in the 75-g OGTT
140-199 mg/dl (7.8-11.0 mmol/l): IGT
or
A1C 5.7-6.4%
*For all three tests, risk is continuous, extending below the lower limit of a range and becoming disproportionately greater at higher
ends of the range.
ADA. I. Classification and Diagnosis. Diabetes Care 2011;34(suppl 1):S13. Table 3.
Recommendations:
Detection and Diagnosis of GDM
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Screening use
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plasma glucose fasting
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and 2 hours after breakfast,
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if abnormal go for 50 gram oral glucose challenge test.
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In pregnant women previously known to have diabetes, and
screening test abnormal go for confirmatory test for
diagnosis of GDM at 24-28 weeks gestation, using a 100
gram glucose- OGTT
Other investigations:
•Serum Urea.
•Serum Creatinine
•Serum Lipid profile: cholesterol; triglyceride; LDL-C;
HDL-C.
•Serum sodium, potassium,
•24 hour urine for: protein; creatinine clearance;
microalbumin;
•Spot urine for microalbumin
•Spot urine for albumin creatinine ratio- ACR
Other investigations and evaluations:
Blood complete picture
•Urine routine examination: glucose; protein/, albumin,
WBC, sp gravity.
•Urine for ketone bodies
•Arterial blood gases-ABG’s
•Ultra sound liver- Fatty liver
•Fundoscopy- for diabetic retinopathy;
•Routine eye exam: diabetic cataract
•Blood pressure measurement
•Examination of feet- ulcer; poor sensations/neuropathy
Thank you