DM-1-fianl - howMed Lectures

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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  MCQ’s

The Miracle of Insulin

Patient J.L., December 15, 1922 February 15, 1923

Diabetes Mellitus

 “Diabetes is a dreadful affliction,---------”.

 Areteus of Cappadosia in 2 nd 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

Diabetes a

global

epidemic

Years 1998 2003 Diabetics (Million) 135 170 2025 Sheikh M.Z, Diabetes Mellitus: The Continuing Challenge, JCPSP 2004 Vol.14(2), 63-64 300

WHO Estimates

WHO ranks Pakistan 7 th on diabetes prevalance list (The Nation ; English Daily- 15 th 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 ,

Diabetes epidemiology in Pakistan

Years 1995 Diabetics (Million) 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

Balochistan

Diabetes

8.4% Kyber Pakhtun Khwa (KPK) Sindh 11.1% 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

Females

8.2%

14.3%

Sheikh M.Z, Diabetes Mellitus: The Continuing Challenge, JCPSP 2004 Vol.14(2) 63-64

SURGE

IN DIABETES MELLITUS

Developing countries > 200%

 Developed countries > 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

Normal Pancreatic Islets:

ß cells Glucagon cells

Insulin Promotes Anabolism

Insulin lowers plasma glucose by: 1.

2.

3.

4.

Increasing glucose transport into most insulin sensitive cells Enhancing cellular utilization and storage of glucose Enhancing utilization of amino acids Promoting fat synthesis

INSULIN

Glucagon Is Dominant In The Fasting State

Glucagon prevents

Glucagon is secreted when plasma glucose levels fall below 100 mg/dL.

The liver hypoglycemia .

is the primary target of glucagon.

Glucagon stimulates glycogeno lysis gluco neo genesis and 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

Putative trigger

-Cell mass 100% Genetic predisposition Cellular autoimmunity Circulating autoantibodies (ICA, GAD65) Insulitis

-Cell injury Loss of first-phase insulin response (IVGTT) Glucose intolerance (OGTT) Clinical onset — only 10% of

-cells remain “Pre” diabetes Diabetes Time Eisenbarth GS. N Engl J Med. 1986;314:1360-1368

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Type 1 DM

Insulinitis

Pathogenesis of Type 2 DM

ß cell defect Genetic Environment Obesity ???

Abnormal Secretion Insulin resistance

Relative Insulin Def.

ß cell exhaustion Type 2 DM IDDM

Is It Gluttony or Sloth??

Jack in the Box

Bacon Ultimate Cheeseburger

1020 Calories 71 grams of Fat Average American child or teen watches 3-4 hours TV per day

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 diabetes Known 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

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Type-1

         Age : < 40 Years Duration : Weeks Ketonuria : Common Insulin Dependent Autoantibody : Yes Family History : No Insulin levels : very low Islets : Insulinitis Complications :  Acute & Metabolic

Type-2

         > 40 Years Months to years Rare Independent * No Yes Normal or high * Normal / Exhaustion Complications  Late and vascular.

I. CLASSIFICATION AND DIAGNOSIS OF DIABETES

Classification of Diabetes 

Type 1 diabetes

 β-cell destruction 

Type 2 diabetes

 Progressive insulin secreting defect 

Other specific types of diabetes

 Genetic defects in β-cell function, insulin action  Diseases of the exocrine pancreas  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 

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

gram glucose- OGTT confirmatory test for diagnosis of GDM at 24-28 weeks gestation, using a 100

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

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