Diabetes Mellitus

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Diabetes Mellitus

• 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
• MCQs

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The Miracle of Insulin
February 15, 1923
Patient J.L., December 15, 1922
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Diabetes Mellitus

• Diabetes is a dreadful affliction,---------.
• Areteus of Cappadosia in 2nd Century.
• 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
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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
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WHO Estimates

• WHO ranks Pakistan 7th on diabetes prevalance
  list- (The Nation English Daily- 15th Nov 2008)
• Pakistan ranked 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 ,
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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
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• 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
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Gender prevalence of DM
Diabetes Mellitus Diabetes Mellitus
Males 16.2
Females 11.7
Impaired Glucose Tolerance Impaired Glucose Tolerance
Males 8.2
Females 14.3
Sheikh M.Z, Diabetes Mellitus The Continuing
Challenge, JCPSP 2004 Vol.14(2) 63-64
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SURGE IN DIABETES MELLITUS

• Developing countries gt 200
• Developed countries gt 45
• Type 2 diabetes, will be 90 of all cases.

Sheikh M.Z, Diabetes Mellitus The Continuing
Challenge, JCPSP 2004 Vol.14(2) 63-64
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Normal Pancreatic Islets
ß cells Glucagon cells
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Insulin Promotes Anabolism

• Insulin lowers plasma glucose by
• Increasing glucose transport into most insulin
  sensitive cells
• Enhancing cellular utilization and storage of
  glucose
• Enhancing utilization of amino acids
• Promoting fat synthesis

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INSULIN
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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.

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GLUCAGON
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Pathogenesis of Type 1DM
Environment ? Viral infe..??
Genetic HLA-DR3/DR4
Autoimmune Insulinitis
ß cell Destruction
Severe Insulin deficiency
Type 1 DM
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Natural History Of PreType 1 Diabetes
Putative trigger
?-Cell mass 100
Cellular autoimmunity
Circulating autoantibodies (ICA, GAD65)
Loss of first-phase insulin response (IVGTT)
Clinical onset only 10 of?-cells remain
Glucose intolerance (OGTT)
Pre-diabetes
Genetic predisposition
Insulitis?-Cell injury
Diabetes
Time
Eisenbarth GS. N Engl J Med. 19863141360-1368
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Insulinitis
Type 1 DM
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Pathogenesis of Type 2 DM
Environment Obesity ???
ß cell defect Genetic
Insulin resistance
Abnormal Secretion
Relative Insulin Def.
ß cell exhaustion
IDDM
Type 2 DM
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Subcutaneous Fat
Gluteal Fat
Viceral Fat
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Islets in Type 2 Diabetes

• Loss of ß cells
• Amyloid deposits
• Hyalinization

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Natural History of Type 2 Diabetes
Impaired glucose tolerance
Undiagnosed diabetes
Known diabetes
Insulin resistance
Insulin secretion
Postprandial glucose
Fasting glucose
Microvascular complications
Macrovascular complications
Adapted from Ramlo-Halsted BA, Edelman SV. Prim
Care. 199926771-789
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Type-1 Type-2

• Age lt 40 Years
• Duration Weeks
• Ketonuria Common
• Insulin- Dependent
• Autoantibody Yes
• Family History No
• Insulin levels very low
• Islets Insulinitis
• Complications
• Acute Metabolic

• gt 40 Years
• Months to years
• Rare
• Independent
• No
• Yes
• Normal or high
• Normal / Exhaustion
• Complications
• Late and vascular.

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I. CLASSIFICATION AND DIAGNOSIS OF DIABETES
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Classification of Diabetes

• Type 1 diabetes
• ß-cell destruction
• Type 2 diabetes
• Progressive insulin secreting defect
• Other specific types of diabetes
• Genetic defects in ß-cell function, insulin
  action
• Diseases of the exocrine pancreas
• Drug- or chemical-induced
• Gestational diabetes mellitus

ADA. I. Classification and Diagnosis. Diabetes
Care 201134(suppl 1)S12.
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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 201134(suppl 1)S13. Table 2.
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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 OGTT140-199 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 201134(suppl 1)S13. Table 3.
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RecommendationsDetection and Diagnosis of GDM

• Screening use
• plasma glucose fasting
• and 2 hours after breakfast,
• if abnormal go for 50 gram oral glucose challenge
  test.
• 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

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• 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

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• Other investigations and evaluations
• Blood complete picture
• Urine routine examination glucose protein/,
  albumin, WBC, sp gravity.
• Urine for ketone bodies
• Arterial blood gases-ABGs
• Ultra sound liver- Fatty liver
• Fundoscopy- for diabetic retinopathy
• Routine eye exam diabetic cataract
• Blood pressure measurement
• Examination of feet- ulcer poor
  sensations/neuropathy

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Thank you