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A global symbol for diabetes

The slogan ‘UNITE FOR DIABETES’

Dr Vijaya Marakala MDvkunder637@gmail.com

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OUR GENES HAVE NOT CHANGED FOR THE PAST 100,000 YEARS

But..we have changed from a primitive hunter-caveman to a sophisticated modern man, especially in the urban areas

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Gains

• Better living conditions• Variety of foods• Better transportation• Better communication

Losses

• More eating• Less physical activity• More stress

Gains and Losses of this transition

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Obesity

Diabetes

Hypertension and cardiovascular diseases

Leading to….

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DIABETES MELLITUS

DefinitionClassificationLab diagnosisRecent aspects

Diabetes Mellitus

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Diabetes Mellitus

A metabolic disorder of multiple aetiology characterized by chronic

hyperglycaemia with disturbances of carbohydrate, fat and protein

metabolism resulting from defects in insulin secretion, insulin action or both .

Definition

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5

15

25

35

45

55

Top 3 countries number of adults with diabetes, 2009In

mill

ions

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One person in the world dying of diabetes every ten seconds.

There will be 2 new diabetic cases in the world being identified every 10sec.

In the national survey 54.1% of diabetes developed it in the most productive years of their lives

IDF predicts that diabetes will cost the world economy at least US$376 billion in 2010, or 11.6% of total world healthcare expenditure.

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Year Author Place Area Prevalence(%)Urban Rural

1971 Tripathy et al Cuttak Central 1.2

1972 Ahuja et al New Delhi North 2.3

1979 Gupta et al Multicentere 3 1.3

1984 Murthy et al Tenali South 4.7

1986 Patel Bhadran West 3.8

1988 Ramachandran et al Kudremukh South 5

1989 Kodali et al Gangavathi South 2.2

1989 Rao et al Eluru South 1.6

1991 Ahuja et al New Delhi North 6.7

1992 Ramachandran et al Madras South 8.2 2.4

1997 Ramachandran et al Madras South 11.6

2000 Ramakutty et al Kerala South 12.4 2.5

2001 Ramachandran et al National DESI 12.1

2001 Mishra et al New Delhi North 10.3

2001 Mohan et al Chennai South 12.1

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WORLD WIDE EPIDEMIC

Zimmet, Nature 2001

India:2000:32 mill2020: 81 mill

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Classification of DIABETES MELLITUS

Type 1

Type 2

Other

Gestational

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Classification of DIABETES MELLITUS

Type 1

β-Cell destruction

Absolute insulin deficiency

Autoantibodies

Type 2 Other Gestational

Islet cell autoantibodiesInsulin autoantibodiesGlutamic acid decarboxylase autoantibodiesTyrosine phosphatase IA-2 and IA-2B b autoantibodies

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Classification of DIABETES MELLITUS

Type 1 Type 2

Insulin resistance with an insulin secretary defectRelative insulin deficiency

Other Gestational

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Classification of DIABETES MELLITUS

Type 1 Type 2 Other Gestational

Associated with secondary conditions

Genetic disease of β-cell function and insulin actionPancreatic diseaseEndocrine diseaseDrug or chemical inducedInsulin receptor abnormalitiesOther genetic syndromes

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Classification of DIABETES MELLITUS

Type 1 Type 2 Other Gestational

Glucose intolerance during pregnancy due to metabolic and hormonal changes

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TYPE 1 DM

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This form of diabetes is immune-mediated in over 90% of cases and idiopathic in less than 10%.

Polyuria, polydipsia, and

weight loss associated with RPG200 mg/dL.

FPG>126 mg/dl more

than one occasion

Islet autoantibodis are frequently

present.

TYPE 1 DM

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Immune-mediated type 1 diabetes mellitus

Approximately one-third of the disease susceptibility is due to genes and two-thirds to environmental factors.

Genes that are related to the HLA locus

contribute about 40% of the genetic risk.

• About 95% of patients with type 1 diabetes possess either HLA-DR3 or HLA-DR4, compared with 45–50% of white controls.

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Immune-mediated type 1DM

Diagnostic sensitivity and specificity of autoimmune markers in patients with newly diagnosed type 1 diabetes mellitus.

Sensitivity Specificity

Glutamic acid decarboxylase (GAD65) 70–90% 99%

Insulin (IAA) 40–70% 99%

Tyrosine phosphatase (IA-2) 50–70% 99%

Most patients with type 1 diabetes mellitus have circulating antibodies to islet cells (ICA), insulin (IAA), glutamic acid decarboxylase (GAD65), and tyrosine phosphatases (IA-2 and IA2-β ) at the time the diagnosis is made.

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Idiopathic type 1 diabetes mellitus

• Less than 10% of subjects have no evidence of pancreatic β cell autoimmunity to explain their insulinopenia and ketoacidosis.

It was recently reported that about 4% of the West Africans with ketosis-prone diabetes are homozygous for a mutation in PAX-4 (Arg133Trp)—a gene that is essential for the development of pancreatic islets.

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Type 2 Diabetes Mellitus

Most patients are over 40 years of age and obese. Polyuria and polydipsia. Ketonuria and weight loss generally are uncommon at time of diagnosis. Candidal vaginitis in women may be an initial manifestation. Many patients have few or no symptoms. Hypertension, dyslipidemia, and atherosclerosis are often associated.

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Other Specific Types of Diabetes Mellitus

Maturity-onset diabetes of the young (MODY)

Autosomal dominant and an age at onset of 25 years or younger.

Nonobese and impaired

glucose-induced secretion of

insulin.

Mutations of a transcription

factor that regulates islet

gene expression.

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This is a very rare subtype of nonobese type 2 diabetes, with no more than ten families having been described.

Since affected individuals were heterozygous and possessed one normal insulin gene, diabetes was mild, did not appear until middle age, and showed autosomal dominant genetic transmission.

Diabetes due to mutant insulins

Other Specific Types of Diabetes Mellitus

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Defects in one of their insulin receptor genes have been found in more than 40 people with diabetes,

and most have extreme insulin resistance associated with acanthosis

nigricans.

Diabetes due to mutant insulin receptors

Other Specific Types of Diabetes Mellitus

Insulin Receptors

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Impairs the transfer of leucine or lysine into mitochondrial proteins has been described.

Most patients have a mild form of diabetes

Diabetes mellitus associated with a mutation of mitochondrial DNA

Other Specific Types of Diabetes Mellitus

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An autosomal recessive neurodegenerative disorder

first evident in childhood.

It is due to mutations in a gene WFS1, which encodes a 100.3 KDa transmembrane protein localized in the ER.

Wolfram's syndrome

Other Specific Types of Diabetes MellitusDIDMOAD

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Insulin Resistance Syndrome (Syndrome X; Metabolic Syndrome)

Individuals are at much higher risk for developing type 2 diabetes than insulin-sensitive persons also elevated plasma triglycerides, lower high-density lipoproteins (HDLs), and higher blood pressure

Twenty-five percent of the general obese nondiabetic population has insulin resistance of a magnitude similar to that seen in type 2 diabetes.

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Gestational Diabetes Mellitus

Occurs during pregnancy as a

result of hormonal influences

causing insulin resistance

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DIABETES MELLITUSInsulin↓ and glucagon↑

↓Glucose uptake Hyperglycemia Glucosuria • Osmotic diuresis• Dehydration• Coma• Death

↑Protein catabolism ↑Plasma amino acids ↑Nitrogen loss in urine

↑Gluconeogenesis

↑Lipolysis ↑FFA oxidation ↑Ketogenesis • Ketosis • Coma• Death

Metabolic events occurring in diabetes mellitus

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Clinical features of diabetes at diagnosis.

Type 1 Diabetes Type 2 Diabetes

Polyuria and thirst ++ +

Weakness or fatigue ++ +

Polyphagia with weight loss ++ –

Recurrent blurred vision + ++

Vulvovaginitis or pruritus + ++

Peripheral neuropathy + ++

Nocturnal enuresis ++ –

Often asymptomatic – ++

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Between 1979-1997Before 1979

No uniform criteria NDDG&WHO

Diagnostic criteria for Diabetes Mellitus

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19991997

ADA WHO

Diagnostic criteria for Diabetes Mellitus

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Since 1965 the WHO has published

guidelines for the diagnosis

and classification of

diabetes.

These were last reviewed in

1998

In addition, in 2003, the ADA

reviewed its diagnostic

criteria.

ADA recommended lowering the

threshold for IFG from 6.1mmol/l (110mg/dl) to

5.6mmol/l(100mg/dl)

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Laboratory Findings

Paper strip impregnated with

glucose oxidase and a chromogen system

Sensitive to as little as 0.1% glucose in urine.

Urinalysis Glucosuria

A normal renal threshold for glucose as well as reliable bladder emptying is essential for interpretation.

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LABORATORY FINDINGS

By nitroprusside tests (Acetest or

Ketostix).

Do not detect β-hydroxybutyric

acid

Urinalysis

Ketonuria

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Laboratory FindingsBlood testing procedures Glucose tolerance test

Normal carbohydrate diet

for 3 days

Overnight fast on the day of the test FPG is drawn

Give 75gm of anhydrous glucose in about 300ml of

water

Blood & urine specimens are

collected at half hourly for 2hours

A curve is plotted for time against blood glucose

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The Diabetes Expert Committee criteria for evaluating the standard oral glucose tolerance test.1

Normal Glucose Tolerance

Impaired Glucose Tolerance

Diabetes Mellitus

Fasting plasma glucose (mg/dL)

< 110 110–125 ≥126

Two hours after glucose load (mg/dL)

< 140 ≥140–199 ≥200

Criteria for laboratory confirmation of diabetes mellitus

Laboratory FindingsBlood testing procedures Glucose tolerance test

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The major form of HbA1 is hemoglobin A1c (HbA1c) where glucose is the carbohydrate.

The remaining HbA1 species contain fructose-1,6 diphosphate (HbA1a1); glucose-6-phosphate (HbA1a2); and unknown carbohydrate moiety (HbA1b).

Glycated hemoglobin (hemoglobin A1) measurements

Laboratory FindingsBlood testing procedures

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Serum fructosamine

Laboratory FindingsBlood testing procedures

Serum fructosamine is formed by nonenzymatic glycosylation of serum proteins (predominantly albumin).

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Self-monitoring of blood glucose

Capillary blood glucose measurements performed by patients themselves, as outpatients, are extremely useful

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Continuous glucose monitoring systems

DexCom system MiniMed system Glucowatch system

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Lipoprotein abnormalities in diabetes

High serum triglyceride level (300–400 mg/dL),

Low HDL cholesterol (less than 30 mg/dL), and

Qualitative change in LDL particles, producing a smaller dense particle

“Diabetic dyslipidemia"

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A European research team has found a molecule, CXCL5, which makes obese people

develop diabetes.

Obese people have large amounts of the molecule CXCL5, produced by certain cells in fatty tissue

"The CXCL5 molecule helps cause insulin resistance and type 2 diabetes".

The finding has been published in the journal Cell Metabolism

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Insulin Pills Likely To Replace Needles

ACS' weekly newsmagazine

Drug manufacturers have tried for years to develop oral insulin without much success.Several insulin pills are now in various stages of clinical trials

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New Insulin To Be Introduced Which Won’t Require Cooling

Bianca van Lierop, Monash University and her colleagues have successfully strengthened insulin's chemical structure, which can withstand higher temperatures.

A development that will bring relief to millions of diabetics across the world.

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New Variants Found That Indicate A Predisposition To Type 2 Diabetes

"Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis,"

Appeared online June 27 in Nature Genetics.

DNA variants that are associated with increased risk of type 2 diabetes, bringing the number to 38.

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From Medscape Medical News HbA1c May Be Useful for Diabetes Screening, Diagnosis in Routine Clinical Practice .Laurie Barclay, MD

January 22, 2010 January 12 issue of Diabetes Care.

Diabetes Care

Study authors write. "A high proportion of people with IA1c [impaired A1c] have abnormal glucose status requiring follow-up."

"HbA1c provides a practical alternative for screening [that] is more convenient and reproducible than is blood glucose.

"HbA1c <5.5% and >7.0% predicts absence or presence of Type 2 diabetes while at HbA1c 6.5-6.9%, diabetes is highly probable in clinical and population settings,"

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PANCREATIC ISLET TRANSPLANTATION

In an experimental procedure called islet transplantation, islets are taken from the pancreas of a deceased organ donor.

The islets are purified, processed, and transferred into another person.

Once implanted, the beta cells in these islets begin to make and release insulin.

Researchers hope that islet transplantation will help people with type 1 diabetes live without daily injections of insulin.

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REFERENCES

CMDT 2010

Standards of Medical Care in Diabetes—2010 American

Diabetes Association

Internet