Diabetes Mellitus an overview. Diabetes is a disorder caused by the presence of too much glucose in...

Diabetes MellitusDiabetes Mellitusan overviewan overview

Diabetes is a disorder caused by the presence of too much glucose in the blood. A first depiction of this “sugar disease” was described in the “Ebers Papyrus”, a papyrus sold to the German Egyptologist Georg Moritz Ebers in 1872. It was said to have been found close to a mummy in the tomb of Thebes and appears to have been written between 3000 and 1500 BC.

HistoryHistoryReference to diabetes was made

1550 BC.In the 2nd Century AD, Aretaeus

gave an excellent description of diabetes.

Thomas Willis in the 17th Century detected the sweet test of urine.

Mathew in the 18th Century showed that the sugar in urine comes from the blood.

HistoryHistoryMinkowski and Von Mering

discovered that disease of the pancreas is responsible for diabetes to develop in the 19th century.

In the 19th century treatment of diabetes was confined to food regulation which reduced urination but did not prevent wasting and complications.

HistoryHistoryIn the second half of the 19th

Century, Paul Langerhans, a German student, identified clusters of cells within the pancreas responsible for the production on glucose lowering substance. “islets of Langerhans”.

Insulin: in Latin insula= island. So the name was coined before the hormone was discovered.

HistoryHistoryBanting and Best “a student”

worked in McLeod's labs in Toronto.

In 1921they made the exocrine cells atrophy by ligation of the pancreatic duct.

They made aqueous extracts of the remaining tissue keeping it cold and filtered it.

The extract was injected into a diabetic dog on 30 July 1921.

HistoryHistory

They convinced themselves that they had discovered the active pancreatic hormone which normalizes the blood sugar.

HistoryHistory

The first person to be treated with insulin was Leonard Thompson (1908-1935). The first injection was in 11 January 1922

History: Noble Prize 1923History: Noble Prize 1923

Banting McLeod

Best Collip

Definition of diabetesDefinition of diabetesA syndrome of chronic

hyperglycaemia with other metabolic abnormalities together with micro and macro-vascular complications.

What is wrong with What is wrong with diabetesdiabetes

Insulin deficiency

Insulin resistanceHyperglycaemia

Classification of diabetesClassification of diabetes

Type 1DMType 2DMIFG: impaired fasting glycaemiaIGT: impaired glucose tolerance GDM: Gestational diabetes mellitusSecondary DM.

Criteria of diagnosisCriteria of diagnosisFBS > 126. MGS%PP > 180 MGS%

normal:FBS - 80 – 100 MGS%PP - 80 – 140 MGS%

T1DMT1DMUsually in young ageCharacterized by absolute insulin

deficiency.Increased catabolism and liability

to ketosis.Stormy presentation.must be treated with insulin.

T2DMT2DMUsually in older age.Relative insulin deficiency.Increased insulin resistance.Can be treated with OHA or

insulin.Slow onset, less likely to develop

ketosis.May present with complications.

MODYMODY

A special type of diabetes similar to type 2 diabetes but develop in young age groups.

Increased prevalence worldwide.Associated with increased

childhood obesity.

Maturity onset diabetes of the youth

Diabetes related to drugsDiabetes related to drugsGlucocorticoidsDiazoxide.Thiazides.PhyentionPentamidine

GDMGDM

Diabetes discovered for the first time during pregnancy.

Every pregnant lady should be screened.

Usually disappears after labor.Increased risk to develop T2DM

later in life.

Gestational diabetes mellitus

Estimated 10 top number of Estimated 10 top number of diabetes patients diabetes patients

DiagnosisDiagnosis

How to diagnose diabetes:1. Signs and symptoms2. Blood glucose test3. OGTT 4. HbA1c

DiagnosisDiagnosisMost people are diagnosed with

diabetes when they are suspected to have symptoms of polyurea, polydepsia, fatigue, loss of weight.

This is confirmed by fasting or PP blood glucose.

In case of doubt OGTT may be done.

Urine testing should not be used in diagnosis.

DiagnosisDiagnosisPeers and medical ‘advisors’ should

be aware of the following:T1DM & T2DM are two distinct

diseases.T1DM is stormy at presentation,

delay in diagnosis can be disastrous.Among the presentations of T1DM

could be some non-specific symptoms like vomiting, abdominal pain….

DiagnosisDiagnosis

T2DM may present with late symptoms, like numpness, disturbed vision, generalized oedema.

Patients with hypertension, dyslipidaemia, MI and family history of diabetes are very likely to develop T2DM.

Pathophysiology of T1DMPathophysiology of T1DM

Absence of insulin secretion

Failure to use glucose as a fuel

Hyperglycaemia & using fat

Ketosis


Possible contributing factors:1. Autoimmune disease.2. HLA typing3. Viruses4. chemicals


Insulin resistance

hyperinsulinaemia

Relative hypoinsulinaemia

Hyperglycaemia, dyslipidaemia, atherosclerosis, HTN

Pathophysiology of T2DMPathophysiology of T2DM Causes of insulin resistance:

1. Hereditary.2. Decreased glucose transporters.3. Decreased insulin receptors4. Post receptor mechanisms5. Chemical mediators e.g. TNFα


Loss of first phase of insulin secretion.

Delayed insulin release.

InsulinInsulin

InsulinInsulin

Action of insulin:1. On glucose metabolism2. On amino acid metabolism3. On lipid metabolism

Insulin Insulin Short acting

InsulinInsulinIntermediate acting

Insulin Insulin Peak less insulinAct for 24 hours no peak

InsulinInsulinPremixed insulin

Insulin Insulin Absorption

Insulin Insulin Variation of absorption:

1. Type2. Dose 3. Site of preparation4. Temperature.5. circulation

InsulinInsulinStorage of insulin

Insulin Insulin

injection

insulininsulin

injection:

insulininsulinDevices

InsulinInsulin

Side effect:1. Hypoglycaemia2. Atrophy3. Hypertrophy4. Sensitivity5. Weight gain

DietDiet

Rules:1. Balanced meal2. Maintain body weight3. Adequate nutrition4. Regular meal time.

DietDiet

OHAOHA

OHAOHA

Sulphonylureas:1. Mode of action2. Side effect3. Differences4. Use

OHAOHA

Metformin:1. Action2. When to use3. Side effects4. Warning.

OHAOHA

Acarbose 1. Action2. Effect3. Side effect use

OHAOHA

Non Sulphonylureas insulin secreatgauges:

1. Repaglinide2. Natiglinide.

OHAOHA

Insulin sensitizers:1. Mode of action2. Effect3. Side effect4. use

SulfonylureasSulfonylurease.g. Chlorpropamide, Glyburidee.g. Chlorpropamide, Glyburide

Mechanism◦Increase insulin secretion by pancreas

Advantages◦Well established, Decrease microvascular

risk, Convenient dosingDisadvantages

◦Hypoglycemia, Weight gainFDA Approval for combination therapy

◦Metformin, TZD, acarbose

Adapted from SE Inzucchi, JAMA 2002; 287:360-372.

Non-SU SecretagoguesNon-SU Secretagoguese.g. Nateglinide, Repaglinidee.g. Nateglinide, Repaglinide

Mechanism◦Increase insulin secretion by pancreas

Advantages◦Targets post-prandial glycemia

Disadvantages◦TID dosing, No long-term data

FDA Approval for combination therapy◦Metformin


BiguanidesBiguanidese.g. Metformine.g. Metformin

Mechanism◦ Decrease hepatic glucose production

Advantages◦ Well established, Weight loss, No hypoglycemia,

Decrease micro & macrovascular risk, Convenient dosing, [Also prevents diabetes]

Disadvantages◦ GI distress, Lactic acidosis, Contraindications

FDA Approval for combination therapy◦ Insulin, SU and non-SU secretagogues, TZD


Alpha-Glucosidase InhibitorsAlpha-Glucosidase Inhibitorse.g. Acarbose, Miglitole.g. Acarbose, Miglitol

Mechanism◦Decrease gut carbohydrate absorption

Advantages◦Targets post-prandial hyperglycemia, No

systemic absorption, [Also prevents diabetes]

Disadvantages◦GI distress, TID dosing, No long-term data

FDA Approval for combination therapy◦Sulfonylureas


ThiazolidindionesThiazolidindionese.g. Pioglitazone, Rosiglitazonee.g. Pioglitazone, Rosiglitazone

Mechanism◦Increase peripheral glucose disposal

Advantages◦Physiologically “correct,” Convenient

dosing, [Also prevents diabetes]Disadvantages

◦Liver toxicity, Liver monitoring, Weight gain, Edema, No long-term data

FDA Approval for combination therapy◦Insulin, sulfonylurea, metformin


Acute complicationsAcute complicationsof Diabetes Mellitusof Diabetes Mellitus

HypoglycaemiaHypoglycaemia

HypoglycaemiaHypoglycaemiaMost common complication of

diabetes◦100% of Type 1 patients affected◦~ 10%/year severe (requiring

assistance)◦much less common in Type 2

Multiple causes:◦exercise/activity drug

overdose◦reduced food intake alcohol use◦delayed meal

Symptoms of Symptoms of HypoglycemiaHypoglycemiaAdrenergic

Neuroglycopenictachycardia dizzinesspalpitations confusionsweating sleepinesstremor comahunger seizure

HypoglycemiaHypoglycemiaSymptoms and SignsSymptoms and Signs

• Sweating, tremors, pounding heart beats.• Pallor, cold sweat, irritability• May develop coma.

63

Prevention of Prevention of HypoglycemiaHypoglycemia

Consistent meal times, appropriate to drug regimen

Consistent carbohydrate intake, or matched to drug dose

Adjustments for extra exercise◦ extra food, e.g. 15 gm carb/30 min◦ reduce drug, e.g. prior dose by 20-30%

Accurate drug dosingBlood glucose monitoring

Treatment of Treatment of HypoglycemiaHypoglycemiaOral carbohydrate:

◦10-15 gms, repeat after 15 minutes if needed

◦glucose tabs preferred; food acts slower, adds unneeded calories (fat, protein)

IV Glucose◦20-50 cc of D50

Glucagon◦1 mg IM

Hyperosmolar Hyperosmolar Hyperglycemic Nonketotic Hyperglycemic Nonketotic SyndromeSyndrome

Hyperosmolar Hyperosmolar Hyperglycemic Nonketotic Hyperglycemic Nonketotic Syndrome Syndrome

Clinical presentationSevere hyperglycemia (BG > 600)No or minimal ketosisHyperosmolarityProfound dehydrationAltered mental status

Causes of HHNSCauses of HHNSDrugs: glucocorticoids, diureticsAcute stressors: infection, burns,

CVA, MI, gastroenteritisOther chronic disease: renal,

heart, old strokeProcedures: surgery

Prevention of HHNSPrevention of HHNS

Awareness of the syndromeMaintenance of adequate

hydrationControl of blood glucose during

acute stress with insulin

DIABETIC KETOACIDOSISDIABETIC KETOACIDOSIS

Diabetic KetoacidosisDiabetic Ketoacidosis

An acute, life threatening metabolic An acute, life threatening metabolic acidosis complicating IDDM and some acidosis complicating IDDM and some cases of NIDDM with intercurrent illness cases of NIDDM with intercurrent illness (infection or surgery)(infection or surgery)

Usually coupled with an increase in Usually coupled with an increase in glucagon concentration with two metabolic glucagon concentration with two metabolic consequences:consequences:◦ 1) Maximal gluconeogenesis with impaired 1) Maximal gluconeogenesis with impaired peripheral utilization of glucoseperipheral utilization of glucose◦ 2) Activation of the ketogenic process and 2) Activation of the ketogenic process and

development of metabolic acidosis.development of metabolic acidosis.

Diabetic KetoacidosisDiabetic KetoacidosisUsually seen in Type 1 DM, but

CAN OCCUR in Type 2Often with acute stress, such as

infection, MI, etc.Recurrent DKA almost always

related to omission of insulin, psychosocial problems

Preventive measures same as for HHNS

Clinical PresentationClinical Presentation

Anorexia, N/V, along with polydepsia and polyuria Anorexia, N/V, along with polydepsia and polyuria for about 24 hrs. followed by stupor (or coma).for about 24 hrs. followed by stupor (or coma).

Abdominal pain and tenderness could be present Abdominal pain and tenderness could be present (remember DDx of acute abdomen).(remember DDx of acute abdomen).

Kussmaul breathing with fruity odor “acetone”Kussmaul breathing with fruity odor “acetone” Sings of dehydration (Sings of dehydration ( HR, postural BP, etc.) HR, postural BP, etc.) Normal or low temperature:Normal or low temperature:

NB.: NB.: if fever is present it suggests infection if fever is present it suggests infection

while leukocytosis alone is not because while leukocytosis alone is not because

DKA per se can cause fever.DKA per se can cause fever.

Has to be treated in HospitalHas to be treated in Hospital

Always refer to EndocrinologistAlways refer to Endocrinologist

•Insulin: is a prerequisite for recoveryInsulin: is a prerequisite for recovery

•IVF: the usual fluid deficit is 3-5LIVF: the usual fluid deficit is 3-5L

•Potassium: replacement is always necessaryPotassium: replacement is always necessary

•Bicarbonate:Bicarbonate:

Acute Complications of Acute Complications of DiabetesDiabetesSUMMARY:

Acute complications can be prevented or greatly reduced

Prevention depends on effective patient education

Chronic complicationsChronic complicationsof Diabetes Mellitusof Diabetes Mellitus

Causes of Death Among People With Causes of Death Among People With DiabetesDiabetes

Ischemic heart diseaseIschemic heart disease

Other heart diseaseOther heart disease

Diabetes (acute complications)Diabetes (acute complications)

CancerCancer

Cerebrovascular diseaseCerebrovascular disease

Pneumonia/influenzaPneumonia/influenza

All other causesAll other causes

CauseCause % of Deaths% of Deaths

Geiss LS et al. In: Diabetes in America. 2nd ed. 1995:233-257.

4040

1515

1313

1313

1010

44

55

Complications of Diabetes: Long termComplications of Diabetes: Long term

◦Macrovascular Ischaemic heart disease – heart attacks;

stroke Peripheral vascular disease – gangrene,

amputations◦ Microvascular

EYE – retinopathy - blindness NERVE - neuropathy (peripheral and

autonomic) KIDNEY – nephropathy; dialysis

◦ Infections

Magnitude of ProblemMagnitude of ProblemDiabetic retinopathy: most

common cause of blindness before age 65

Nephropathy: most common cause of ESRD

Neuropathy: most common cause of non-traumatic amputations

2-3 fold increase in cardiovascular disease

Microvascular Microvascular ComplicationsComplications

Diabetic retinopathy background retinopathy macular edema proliferative retinopathy

Diabetic nephropathyDiabetic neuropathy

distal symmetrical polyneuropathy mononeuropathy (peripheral, cranial nerves) autonomic neuropathy

chronic chronic complications* complications* population based - Egyptianspopulation based - Egyptians

• prevalence known D new D %

– retinopathy 41.5 15.7– nephrop. 6.7 6.8– neuropathy 21.9 13.6– foot ulcers 0.8 0.8

• associationsret; nephr; neuro : glucose

*microvasc + neuropathic; n: 1451

Retinopathy and Blindness in Retinopathy and Blindness in Diabetes PatientsDiabetes Patients

◦ It is estimated that retinopathy affects 80%97% of patients with diabetes of 15 years’ duration

◦ Diabetes is the leading cause of new cases of blindness in adults*

◦ Diabetic retinopathy accounts for the majority of these cases

◦ Minimum cost of blindness for working-age adult is estimated at $12,769 per year

Klein R, Klein BEK. In: Klein R, Klein BEK. In: Diabetes in America. Diabetes in America. 2nd ed.2nd ed. 1995:293-338.1995:293-338.

*Blindness is defined as visual acuity *Blindness is defined as visual acuity 20/20020/200

Diabetic RetinopathyDiabetic RetinopathyBackground retinopathy

◦present in 90% of patients after 10 years

◦asymptomatic◦red dots (microaneurysms)◦dot, blot, and flame shaped

hemorrhages◦hard waxy exudates of lipid and protein◦best detected by dilated eye exam or

photos

Background RetinopathyBackground Retinopathy

Diabetic RetinopathyDiabetic RetinopathyMacular edema

◦sight threatening edema of the macula

◦usually reduces visual acuity early◦can only be diagnosed by

ophthalmologic exam◦focal photocoagulation reduces risk

of blindness by 50%

Diabetic RetinopathyDiabetic Retinopathy

Proliferative retinopathy◦growth of small, fragile blood vessels

that may bleed (vitreous hemorrhage)◦associated with growth of fibrous tissue

that may cause retinal detachment◦may occur on the optic disk or elsewhere◦high risk of blindness (50% in 3 years)◦hypertension, isometric exercise, high

contact sports may increase risk of bleeding

Preproliferative RetinopathyPreproliferative Retinopathy

Kidney Disease in Diabetes PatientsKidney Disease in Diabetes Patients

◦ 27,851 new cases of ESRD in diabetes patients in 1995

40% of all new cases in the US

◦ Nearly 99,000 diabetes patients required dialysis or kidney transplantation that year

◦ Annual cost of ESRD: $45,000 in diabetic patients ages 4564

National Diabetes Fact Sheet. National Diabetes Fact Sheet. November 1, 1997:1-8.November 1, 1997:1-8.U.S. Renal Data System, U.S. Renal Data System, USRDS 1997 Annual Data ReportUSRDS 1997 Annual Data Report..

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