Diabetes MellitusDiabetes Mellitus

Global and national prevalence of Global and national prevalence of diabetesdiabetes

Types of diabetesTypes of diabetes Pathogenesis of diabetesPathogenesis of diabetes Classification and criteria for lab Classification and criteria for lab

diagnosis of diabetesdiagnosis of diabetes Lab investigations for a patient of Lab investigations for a patient of

diabetesdiabetes MCQ’sMCQ’s

Patient J.L., December 15, 1922

February 15, 1923

The Miracle of The Miracle of InsulinInsulin

Diabetes MellitusDiabetes Mellitus

““Diabetes is a dreadful Diabetes is a dreadful

affliction,---------”. affliction,---------”.

Areteus of Cappadosia in 2Areteus of Cappadosia in 2ndnd Century. Century.

It continues to be a sinister disease, if It continues to be a sinister disease, if

not taken care of.not taken care of.

Sheikh M.Z, Diabetes Mellitus: The Continuing Challenge,

JCPSP 2004 Vol.14(2), 63-64

Diabetes a Diabetes a globalglobal epidemic epidemic

YearsYears Diabetics Diabetics (Million) (Million)

19981998 135135

20032003 170170

20252025 300300Sheikh M.Z, Diabetes Mellitus: The Continuing Challenge,

JCPSP 2004 Vol.14(2), 63-64

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 ,

WHO Estimates

Diabetes Diabetes epidemiologyepidemiology in in PakistanPakistan

YearsYears Diabetics Diabetics (Million)(Million)

19951995 4.34.3

20252025 14.514.5

Sheikh M.Z, Diabetes Mellitus: The Continuing Challenge,

JCPSP 2004 Vol.14(2) 63-64

The provincial prevalence of diabetes The provincial prevalence of diabetes mellitus- Pakistanmellitus- Pakistan

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

Province Province DiabetesDiabetes

BalochistanBalochistan 8.4%8.4%

Kyber Pakhtun Khwa Kyber Pakhtun Khwa (KPK)(KPK)

11.1%11.1%

SindhSindh 13.9%13.9%

Punjab*Punjab* 10.910.9

GenderGender prevalence of prevalence of DMDM

Sheikh M.Z, Diabetes Mellitus: The Continuing Challenge,

JCPSP 2004 Vol.14(2) 63-64

Diabetes MellitusDiabetes Mellitus

MalesMales 16.2%16.2%

FemalesFemales 11.7%11.7%

Impaired Glucose Tolerance

MalesMales 8.2%8.2%

Females 14.3%

SURGESURGE IN DIABETES MELLITUS IN DIABETES MELLITUS

Developing countriesDeveloping countries > 200%> 200%

Developed countries > 45%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:Normal Pancreatic Islets:

ß cells ß cells Glucagon cellsGlucagon 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 Pathogenesis of Type 1DM1DM

Environment ?Environment ?

Viral infe..??Viral infe..??Genetic Genetic

HLA-DR3/DR4HLA-DR3/DR4

Severe Insulin deficiencySevere Insulin deficiency

ß cell Destructionß cell Destruction

Type 1 DMType 1 DM

Autoimmune Insulinitis Autoimmune Insulinitis

Putativetrigger

Circulating autoantibodies (ICA, GAD65)

Cellular autoimmunityCellular autoimmunity

Loss of first-phase insulin response (IVGTT)

Glucose intolerance (OGTT)

Clinicalonset—

only 10% of-cells remain

Time

-Cell mass 100%

“Pre”-diabetes

Geneticpredisposition

Insulitis-Cell injury

Eisenbarth GS. N Engl J Med. 1986;314:1360-1368

Diabetes

Natural History Of “Pre”–Type 1 Natural History Of “Pre”–Type 1 DiabetesDiabetes

14

InsulinitisInsulinitis

Type 1 DM

Pathogenesis of Type 2 Pathogenesis of Type 2 DMDM

EnvironmentEnvironment

Obesity ???Obesity ???ß cell defectß cell defect

GeneticGenetic

ß cell ß cell

exhaustionexhaustion Type 2 DMType 2 DM

Insulin resistanceInsulin resistance

Relative Insulin Def.Relative Insulin Def.

IDDMIDDM

Abnormal SecretionAbnormal Secretion

J ack in the Box

Bacon Ultimate Cheeseburger

1020 Calories

71 grams of Fat

Average American

child or teen

watches 3-4 hours TV per day

I s I t Gluttony or Sloth??

H4046

Subcutaneous Fat Gluteal Fat Viceral Fat

Islets in Type 2 Diabetes:Islets in Type 2 Diabetes:

Loss of ß cellsLoss of ß cellsAmyloid depositsAmyloid depositsHyalinizationHyalinization

Adapted from Ramlo-Halsted BA, Edelman SV. Prim Care. 1999;26:771-789

Natural History of Type 2 Natural History of Type 2 DiabetesDiabetes

Macrovascular complicationsMicrovascular complications

Insulin resistanceInsulin resistance

ImpairedImpairedglucose toleranceglucose tolerance

UndiagnosedUndiagnoseddiabetesdiabetes Known diabetesKnown diabetes

Insulin secretionInsulin secretion Postprandial glucose

Fasting glucoseFasting glucose

17

Type-1Type-1 Type-2Type-2 AgeAge: < 40 Years: < 40 Years DurationDuration: Weeks: Weeks KetonuriaKetonuria: Common: Common Insulin-Insulin- Dependent Dependent AutoantibodyAutoantibody: Yes: Yes Family HistoryFamily History: No: No Insulin levelsInsulin levels: very : very

lowlow IsletsIslets: Insulinitis: Insulinitis ComplicationsComplications: :

Acute & MetabolicAcute & Metabolic

> 40 Years> 40 Years Months to yearsMonths to years RareRare Independent *Independent * NoNo YesYes Normal or high *Normal or high * Normal / ExhaustionNormal / Exhaustion ComplicationsComplications

Late and vascular. Late and vascular.

I. CLASSIFICATION AND I. CLASSIFICATION AND DIAGNOSIS OF DIABETESDIAGNOSIS OF DIABETES

Classification of DiabetesClassification of Diabetes

Type 1 diabetesType 1 diabetes ββ-cell destruction-cell destruction

Type 2 diabetesType 2 diabetes Progressive insulin secreting defectProgressive insulin secreting defect

Other specific types of diabetesOther specific types of diabetes Genetic defects in Genetic defects in ββ-cell function, insulin action-cell function, insulin action

Diseases of the exocrine pancreasDiseases of the exocrine pancreas

Drug- or chemical-inducedDrug- or chemical-induced

Gestational diabetes mellitusGestational diabetes mellitus

ADA. I. Classification and Diagnosis. Diabetes Care 2011;34(suppl 1):S12.

Criteria for the Diagnosis of DiabetesCriteria for the Diagnosis of Diabetes

HbA1CHbA1C ≥6.5% ≥6.5%OROR

Fasting plasma glucose (FPG)Fasting plasma glucose (FPG)≥126 mg/dl (7.0 mmol/l)≥126 mg/dl (7.0 mmol/l)

OROR

Two-hour plasma glucose ≥200 mg/dl (11.1 Two-hour plasma glucose ≥200 mg/dl (11.1 mmol/lmmol/l) during an OGTT) during an OGTT

OROR

A random plasma glucoseA random plasma glucose ≥200 mg/dl (11.1 ≥200 mg/dl (11.1 mmol/l)mmol/l)

ADA. I. Classification and Diagnosis. Diabetes Care 2011;34(suppl 1):S13. Table 2.

Prediabetes: IFG, IGT, Increased A1CPrediabetes: IFG, IGT, Increased A1C

Categories of increased risk for diabetes Categories of increased risk for diabetes (Prediabetes)*(Prediabetes)*

FPGFPG 100-125 mg/dl 100-125 mg/dl (5.6-6.9 mmol/l)(5.6-6.9 mmol/l): IFG: IFG

oror

2-h plasma glucose in the 75-g OGTT2-h plasma glucose in the 75-g OGTT140-199 mg/dl (7.8-11.0 mmol/l): IGT140-199 mg/dl (7.8-11.0 mmol/l): IGT

oror

A1C 5.7-6.4%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:Recommendations:Detection and Diagnosis of GDMDetection and Diagnosis of GDM

ScreeningScreening use use plasma glucose fasting plasma glucose fasting and 2 hours after breakfast,and 2 hours after breakfast, if abnormal go for 50 gram oral glucose if abnormal go for 50 gram oral glucose

challenge test.challenge test.

In pregnant women previously known to have diabetes, In pregnant women previously known to have diabetes, and and screening test abnormal go for 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

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