diabetes mellitus an overview. diabetes is a disorder caused by the presence of too much glucose in...
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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
Pathophysiology of T1DMPathophysiology of T1DM
Possible contributing factors:1. Autoimmune disease.2. HLA typing3. Viruses4. chemicals
Pathophysiology of T2DMPathophysiology of T2DM
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
Pathophysiology of T2DMPathophysiology of T2DM
Loss of first phase of insulin secretion.
Delayed insulin release.
InsulinInsulin
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
Adapted from SE Inzucchi, JAMA 2002; 287:360-372.
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
Adapted from SE Inzucchi, JAMA 2002; 287:360-372.
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
Adapted from SE Inzucchi, JAMA 2002; 287:360-372.
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
Adapted from SE Inzucchi, JAMA 2002; 287:360-372.
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..