Diabetes Mellitus Diabetes Mellitus in Childrenin Children

DMDM Type IType I

Olena Riga Olena Riga

KhNMUKhNMU

Diabetes MellitusDiabetes Mellitus

DM is a DM is a syndromesyndrome of disturbed of disturbed energy metabolism caused by energy metabolism caused by deficiency of deficiency of Ins Ins secretion or secretion or InsIns action at the cellular level that action at the cellular level that results in altered fuel homeostasis results in altered fuel homeostasis affecting carbohydrate, protein, affecting carbohydrate, protein, and fat.and fat.

World StatisticsWorld Statistics

246.000.000246.000.000 patients with DM in patients with DM in the World were reiterated at 2006 yrthe World were reiterated at 2006 yr

380.000.000380.000.000 – prognosis for 2025 – prognosis for 2025 yryr

Every 10 seconds one Every 10 seconds one patient die from DMpatient die from DM

World StatisticsWorld Statistics

Every years the DM type I Every years the DM type I occurs in occurs in 70 00070 000 children children

EURODIAB: every year EURODIAB: every year increasing DM type I in increasing DM type I in adults adults in 3%in 3% and and in 4.8%in 4.8% in in children children

(на 1000 населения)

0

0,1

0,2

0,3

0,4

0,5

0,6

0,7

Mortality from DM type IMortality from DM type IMortality DM type IMortality DM type I (1922(1922--1972)1972)from 90% to 50%from 90% to 50%

1922 г.1922 г.1922 г. 1972 г.1972 г.1972 г.

Green A. // Diabetologia. – 1985., 28: 339 - 42Green A. // Diabetologia. Green A. // Diabetologia. –– 1985., 28: 339 1985., 28: 339 -- 4242

Снизилась на 40%СнизиласьСнизилась на 40%на 40%Decrease on the Decrease on the 40%40%

Historical DataHistorical Data

Increasing of the urination was Increasing of the urination was described 1500 yrs B.C. at Egyptdescribed 1500 yrs B.C. at Egypt

Fist clinical description of the DM by Fist clinical description of the DM by Cels (30-50 yrs Anno Domini)Cels (30-50 yrs Anno Domini)

The term “Diabayo” – passing The term “Diabayo” – passing through (30-90 yrs Anno Domini)through (30-90 yrs Anno Domini)

1600 yr – the term “mellitus” (lat)- 1600 yr – the term “mellitus” (lat)- honey due to sweet urine tastehoney due to sweet urine taste

Historical Data (c’d)Historical Data (c’d)

1674 yr Tomas Willis (Oxford) 1674 yr Tomas Willis (Oxford) supposed that the sugar pass to urine supposed that the sugar pass to urine from bloodfrom blood

1841-1848 yrs Trommer and Felling – 1841-1848 yrs Trommer and Felling – methodic of the definition of blood methodic of the definition of blood sugar by Copper Oxidesugar by Copper Oxide

1796 Rallo at first proposed to restrict 1796 Rallo at first proposed to restrict the carbohydrate intake to patients the carbohydrate intake to patients with DM with DM

Historical Data (c’d)Historical Data (c’d)

1813-1878 yrs Klod Bernar 1813-1878 yrs Klod Bernar discribed the pathogenesis discribed the pathogenesis of hyperglycemiaof hyperglycemia

1869 yr 1869 yr medical studentmedical student Paul LangerhansPaul Langerhans discovered the cells discovered the cells congestion in pancreascongestion in pancreas

1874 yr Kussmaul discovered 1874 yr Kussmaul discovered ketons, aceton, described ketons, aceton, described specific type of breathingspecific type of breathing

Historical Data (c’d)Historical Data (c’d)

1989 yr Mering & Minkovsky 1989 yr Mering & Minkovsky established that the dogs with established that the dogs with pancrectomy develops hyperglycemia pancrectomy develops hyperglycemia and further deathand further death

1902 yr Opy – described the 1902 yr Opy – described the degeneration of the Langergans isletdegeneration of the Langergans islet

1907 yr Lane Bersley (Chicago) 1907 yr Lane Bersley (Chicago) discovered pancreatic cells type A discovered pancreatic cells type A and type B and type B

Historical Data (c’d)Historical Data (c’d)

1955 yr Sanger 1955 yr Sanger (Cambridge) –(Cambridge) –discovery discovery aminoacid aminoacid structure in structure in molecular of Insmolecular of Ins

С-С-peptide is the predecessor of peptide is the predecessor of Ins Ins 1969 yr Steiner – invented 1969 yr Steiner – invented biosynthesis of the C-peptidebiosynthesis of the C-peptide

1973 yr mono component - Ins 1973 yr mono component - Ins was synthesizedwas synthesized

Etiologic classification of DMEtiologic classification of DM

I. I. Type I DMType I DM ( (ββ-cell destruction, -cell destruction, usually leading to absolute Ins usually leading to absolute Ins deficiency)deficiency)

II. Type II DMII. Type II DM (may rang from (may rang from predominantly Ins resistance predominantly Ins resistance with relative Ins deficiency to a with relative Ins deficiency to a predominantly receptor defect predominantly receptor defect with with InsIns resistance) resistance)

Etiologic classification of DM Etiologic classification of DM (c’d) III. (c’d) III. Other specific typesOther specific types

A.A. Monogenic DMMonogenic DM

B.B. Exocrine pathology of pancreasExocrine pathology of pancreas

C.C. Endocrine diseasesEndocrine diseases

D.D. DrugsDrugs

E.E. Genetics syndromes such as Down, Genetics syndromes such as Down, Turner etc. Turner etc.

The onset DM The onset DM type I occurs type I occurs predominantly predominantly in childhood, in childhood, with median age with median age of 7 to 15 yrs, of 7 to 15 yrs, but it may but it may present at any present at any ageage

DM type IDM type I

DM type I is DM type I is characterized characterized by by autoimmune autoimmune destruction destruction of pancreatic of pancreatic ββ-cells-cells

DM type IDM type I

ΒΒ-cells -cells destruction destruction may be due to may be due to drugs, viruses, drugs, viruses, mitochondrial mitochondrial defects, defects, ionizing ionizing radiation, etcradiation, etc

DM (DM I type)DM (DM I type) Genetic susceptibility to type I DM Genetic susceptibility to type I DM

is controlled by alleles of the is controlled by alleles of the major hystocompatability complex major hystocompatability complex class II genes expressing human class II genes expressing human leukocyte antigens (HLA) that leukocyte antigens (HLA) that associated with antibodies to associated with antibodies to glutamatic acid decarboxylaseglutamatic acid decarboxylase DM I type is associated with other DM I type is associated with other autoimmune diseases such as autoimmune diseases such as thyroiditis, Celiac disease, thyroiditis, Celiac disease, multiply sclerosis, Addison multiply sclerosis, Addison disease, and etc.disease, and etc.

Manifestation of the DM if the Manifestation of the DM if the 80-90% betta cells were 80-90% betta cells were

destructeddestructed

DM II type –resistant to InsDM II type –resistant to Ins

Etiologic classification of DM Etiologic classification of DM (c’d) III. (c’d) III. Other specific typesOther specific types

Genetic defects of Genetic defects of ββ-cell function-cell function chromosome 12, chromosome 12, HNF-1HNF-1άά - MODY-3- MODY-3

chromosome 7, chromosome 7, glucokinase,glucokinase, MODY-2 MODY-2

chromosome 20, chromosome 20, HNF-4HNF-4άά - MODY-1 - MODY-1

Mitochondrial DNAMitochondrial DNA

MODY- maturity-onset diabetes of the MODY- maturity-onset diabetes of the young young *HNF –hepatocyte nuclear factor *HNF –hepatocyte nuclear factor gene mutation gene mutation

Etiologic classification of DM Etiologic classification of DM (c’d) III. (c’d) III. Other specific typesOther specific types

Genetic defects in Genetic defects in Ins actionIns action

Type A Ins resistanceType A Ins resistanceLeprechaunismLeprechaunismRabson-Mendenhall Rabson-Mendenhall

syndromesyndromeLipoatropic diabetesLipoatropic diabetes(Lorens syndrome)(Lorens syndrome)

Type AType A

AdolescenceAdolescence Ins-resistance in absence of obesityIns-resistance in absence of obesity Acanthosis NigricansAcanthosis Nigricans Androgen Excess & HypertrichosisAndrogen Excess & Hypertrichosis Gene involved Insulin receptorGene involved Insulin receptor RecessiveRecessive

LeprechaunismLeprechaunism CongenitalCongenital Abnormal facesAbnormal faces Large genitaliaLarge genitalia SGA and growth retardationSGA and growth retardation Rarely survive infancyRarely survive infancy Acanthosis NigricansAcanthosis Nigricans Gene involvedGene involved Insulin receptor & GH-Insulin receptor & GH-

resistenceresistence RecessiveRecessive

LeprechaunismLeprechaunism

Rabson-MendenhallRabson-Mendenhall

CongenitalCongenital Extreme Growth retardationExtreme Growth retardation Abnormal dentitionAbnormal dentition Acanthosis NigricansAcanthosis Nigricans Androgen Excess & HypertrichosisAndrogen Excess & Hypertrichosis Gene involved Insulin receptorGene involved Insulin receptor RecessiveRecessive

LipodystrophyLipodystrophy Lorens syndromeLorens syndrome

Congenital or AdolescenceCongenital or Adolescence Loss of subcutaneous fat – partial or Loss of subcutaneous fat – partial or

totaltotal Acanthosis NigricansAcanthosis Nigricans Androgen Excess & HypertrichosisAndrogen Excess & Hypertrichosis Gene involvedGene involved Total: Seipin & AGPAT2Total: Seipin & AGPAT2

(recessive) (recessive) Partial :Lamin AC & PPARG Partial :Lamin AC & PPARG (dominant(dominant))

The key feature of all insulin The key feature of all insulin resistance syndromes are acanthosis resistance syndromes are acanthosis nigricans, androgen excess and nigricans, androgen excess and massively raised insulin massively raised insulin concentrations in the absence of concentrations in the absence of obesity obesity

Maternal transmission of mutated or Maternal transmission of mutated or deleted mitochondrial DNA (mtDNA) deleted mitochondrial DNA (mtDNA)

and the mitochondrial tRNA (leu(UUR)) and the mitochondrial tRNA (leu(UUR)) gene (B) can result in maternally gene (B) can result in maternally

inherited diabetes.inherited diabetes.MELAS syndrome: MELAS syndrome:

mitochondrial myopathymitochondrial myopathy EncephalopathyEncephalopathy lactic acidosis lactic acidosis stroke-like syndromestroke-like syndrome

Mitochondrial diabetes is commonly Mitochondrial diabetes is commonly associated with sensorineural deafness and associated with sensorineural deafness and short stature. The diabetes is characterised short stature. The diabetes is characterised by progressive non-autoimmune beta-cell by progressive non-autoimmune beta-cell failure and may progress to needing insulin failure and may progress to needing insulin treatment rapidly.treatment rapidly.

Etiologic classification of DM Etiologic classification of DM (c’d) III. (c’d) III. Other specific typesOther specific types

Diseases of the exocrine pancreasDiseases of the exocrine pancreasPancreatitisPancreatitisTrauma, pancreatomyTrauma, pancreatomyNeoplasiaNeoplasiaCystic fibrosisCystic fibrosisHemochromatosisHemochromatosisFibrocalculous pancreatopathyFibrocalculous pancreatopathyPancreatic resectionPancreatic resection

Etiologic classification of DM Etiologic classification of DM (c’d) III. (c’d) III. Other specific typesOther specific types

EndocrinopathiesEndocrinopathies

AcromegalyAcromegalyCushing diseaseCushing diseaseGlucagonomaGlucagonomaPheochromocytomPheochromocytom

aaHyperthyroidismHyperthyroidismSomatostatinomaSomatostatinomaAldosteronomaAldosteronoma

Etiologic classification of DM Etiologic classification of DM (c’d) III. (c’d) III. Other specific typesOther specific types

InfectionsInfections

Congenital rubellaCongenital rubella

CytomegalovirusCytomegalovirus

Hemolitic-uremic Hemolitic-uremic syndrome syndrome →→→→→→

Etiologic classification of DM Etiologic classification of DM (c’d) III. (c’d) III. Other specific typesOther specific types

Genetic syndromesGenetic syndromesDown syndromeDown syndromeKlinefelter syndromeKlinefelter syndromeWolfram syndromeWolfram syndromeFriedreich ataxiaFriedreich ataxiaHuntington choreaHuntington choreaLaurence-Moon & Bardet-Laurence-Moon & Bardet-

Biedl syndromeBiedl syndromeMyotonic distrophyMyotonic distrophyPorphyriaPorphyriaPrader-Willi syndromePrader-Willi syndrome

Wolfram syndrome Wolfram syndrome (DIDMOAD)(DIDMOAD)

DI-diabetes insipidusDI-diabetes insipidus

DM-diabetes mellitusDM-diabetes mellitus

OA-optical atrophyOA-optical atrophy

D- deafnessD- deafness

????????

Prader-Willi syndromePrader-Willi syndrome

Etiologic classification of DM Etiologic classification of DM (c’d)(c’d)

III. III. Other specific typesOther specific types Gestational DMGestational DM Neonatal DMNeonatal DM

Neonatal diabetesNeonatal diabetes

There is good evidence that diabetes There is good evidence that diabetes diagnosed in the first 6 months is not diagnosed in the first 6 months is not Type I DM as neither autoantibodies Type I DM as neither autoantibodies nor an excess of high Type I HLA nor an excess of high Type I HLA susceptibility are found in these susceptibility are found in these patients.patients.

Neonatal diabetes is insulin requiring Neonatal diabetes is insulin requiring diabetes which is usually diagnosed diabetes which is usually diagnosed in the first three months of life.in the first three months of life.

Neonatal diabetesNeonatal diabetes

Clinically two Clinically two subgroups were subgroups were

recognized: recognized: transient neonatal transient neonatal diabetes mellitus diabetes mellitus

(TNDM) & (TNDM) & permanent permanent

neonatal diabetes neonatal diabetes mellitus (PNDM)mellitus (PNDM)

Transient neonatal Transient neonatal diabetesdiabetes anomalies on 6q24 anomalies on 6q24 locus locus

DM associated within the first week and DM associated within the first week and resolves around 12 weeks resolves around 12 weeks

50% of cases DM will reoccur during the 50% of cases DM will reoccur during the paediatric age range paediatric age range

Macroglossia seen in 23% Macroglossia seen in 23% Initial glucose values can be very high Initial glucose values can be very high

(range12-57 mmol/L) and so insulin is used (range12-57 mmol/L) and so insulin is used initially although the dose can rapidly be initially although the dose can rapidly be reduced. reduced.

The response to oral treatment such as The response to oral treatment such as sulphonylureas or metformin is uncertainsulphonylureas or metformin is uncertain

Permanent neonatal Permanent neonatal diabetesdiabetes

Kir6.2 mutationsKir6.2 mutations Only 10% have a remitting form of DM that Only 10% have a remitting form of DM that

may latter relapsemay latter relapse Most patients have isolated DM Most patients have isolated DM 20% have developmental delay of motor and 20% have developmental delay of motor and

social function & generalized epilepsy so social function & generalized epilepsy so called DEND syndrome Developmental called DEND syndrome Developmental delay, Epilepsy and Neonatal Diabetes delay, Epilepsy and Neonatal Diabetes

Patients have all the clinical features of Patients have all the clinical features of insulin dependency do not have detectable C insulin dependency do not have detectable C peptide. It has been shown that these peptide. It has been shown that these patients can not be successfully treated with patients can not be successfully treated with oral sulphonylureas. oral sulphonylureas.

Etiologic classification of DM Etiologic classification of DM (c’d) III. (c’d) III. Other specific typesOther specific types

Drug- or chemical-inducedDrug- or chemical-induced

Pentamidine, Nicotinic acidPentamidine, Nicotinic acid

GlucocorticoidsGlucocorticoids

Thyroid hormoneThyroid hormone

ßß-adrenergic agonists-adrenergic agonists

ThiasidesThiasides

ΒΒ-Interferon & others-Interferon & others

InsulinInsulin

InsIns is synthesized on the ribosoms of is synthesized on the ribosoms of pancreatic islet beta cells and is pancreatic islet beta cells and is released into the circulation as a released into the circulation as a molecule comprised of two separate molecule comprised of two separate straight polypeptide chains linked by straight polypeptide chains linked by disulfide bridges between and within disulfide bridges between and within these chains these chains

InsIns is the major anabolic is the major anabolic hormone of the bodyhormone of the body

InsIns action is on action is on target cells in target cells in tissues such tissues such as liver, as liver, adipocytes adipocytes and muscleand muscle

Metabolic events during the Metabolic events during the fed and fasted states (liver)fed and fasted states (liver)

High-Ins (fed) &High-Ins (fed) & Low Ins Low Ins (fasted)state(fasted)state

Glucose uptake Glucose Glucose uptake Glucose productionproduction

Glycogen synthesis GlycogenolysisGlycogen synthesis Glycogenolysis

Absent gluconeogenesis Present G-sisAbsent gluconeogenesis Present G-sis

Lipogenesis Absent l-sisLipogenesis Absent l-sis

Absent ketogenesis KetogenesisAbsent ketogenesis Ketogenesis

Metabolic events during the Metabolic events during the fed and fasted states (muscle)fed and fasted states (muscle)

High-Ins (fed) &High-Ins (fed) & Low Ins (fasted)stateLow Ins (fasted)state

Glucose uptake Absent glucose uptake Glucose uptake Absent glucose uptake

Glucose oxidation Fatty acid Glucose oxidation Fatty acid άάketooxydationketooxydation

Glycogen synthesis GlycogenolysisGlycogen synthesis Glycogenolysis

Protein syntesis Proteolysis and amino Protein syntesis Proteolysis and amino acid releaseacid release

Metabolic events during the Metabolic events during the fed and fasted states (Adipose fed and fasted states (Adipose

tissue)tissue)High-Ins (fed) &High-Ins (fed) & Low Ins Low Ins

(fasted)state(fasted)state

Glucose uptake Absent Glucose Glucose uptake Absent Glucose uptake uptake

Lipid synthesis Lipid synthesis Lipolysis and fatty Lipolysis and fatty acid acid release release

Triglyceride uptake Absent triglyceride Triglyceride uptake Absent triglyceride uptakeuptake

Pathophysiology of DM type Pathophysiology of DM type II

Progressive destruction of Progressive destruction of ββ-cells -cells leads to progressively more severe leads to progressively more severe Ins deficiency with involving classical Ins deficiency with involving classical stress hormones (epinephrine, stress hormones (epinephrine, cortisol, growth hormone, and cortisol, growth hormone, and glucagon) so called counter-glucagon) so called counter-regulatory hormonesregulatory hormones

Ins deficiency, acting in Ins deficiency, acting in concert with the excessive concert with the excessive concentration of epinephrine, concentration of epinephrine, cortisol, growth hormone, and cortisol, growth hormone, and glucagon will result in glucagon will result in unrestrained glucose unrestrained glucose production while glucose production while glucose utilization is impaired, so that utilization is impaired, so that hyperglycemia hyperglycemia develops.develops.

Ins deficiency and elevating Ins deficiency and elevating counter-regulatory hormones counter-regulatory hormones leads to lipolysis and leads to lipolysis and impaired lipid synthesis and impaired lipid synthesis and elevation in plasma total elevation in plasma total lipids, cholesterol, lipids, cholesterol, triglycerids, and free fatty triglycerids, and free fatty acids.acids.

The hormonal interplay of Ins The hormonal interplay of Ins deficiency and glucagon deficiency and glucagon excess shunts the free fatty excess shunts the free fatty acids to ketone body acids to ketone body formationformation

AcetoneAcetone

AcetoacetateAcetoacetate

ΒΒ-oxyoil acid-oxyoil acid

Accumulation of ketoacids results in Accumulation of ketoacids results in metabolic acidosis and the metabolic acidosis and the compensatory rapid deep breathing, compensatory rapid deep breathing, which is an attempt to excrete which is an attempt to excrete excess COexcess CO2 2 (Kussmaul’s respiration)(Kussmaul’s respiration)

Acetone, formed by nonenzymatic Acetone, formed by nonenzymatic conversation of acetoacetate, is conversation of acetoacetate, is responsible for the characteristic responsible for the characteristic fruity odor of the breathfruity odor of the breath

Ketones are readily excreted in the Ketones are readily excreted in the urine in association with cations, urine in association with cations, further compounding losses of water further compounding losses of water and electrolytes (dehydration)and electrolytes (dehydration)

With progressive dehydration, With progressive dehydration, acidosis, hyperosmolality, and acidosis, hyperosmolality, and diminished cerebral oxygen utilization, diminished cerebral oxygen utilization, consciousness becomes imparired and consciousness becomes imparired and ultimately results in coma.ultimately results in coma.

DMDM

The loss of weight is on the basis of The loss of weight is on the basis of the catabolic state and urinary losses the catabolic state and urinary losses of calories due to polyuriaof calories due to polyuria

The no effective calories balance The no effective calories balance lead to the hunger & polyphagia lead to the hunger & polyphagia (despite the increase food intake (despite the increase food intake calories cannot be utilized) & weight calories cannot be utilized) & weight loss occursloss occurs

DMDM

Glucosuria results when the renal Glucosuria results when the renal threshold of threshold of ≈ 160 ml/dl ≈ 160 ml/dl ( (> 8.88 > 8.88 mmmol/L) mol/L) is exceeded; the resultant is exceeded; the resultant osmotic diuresis produces polyuria, osmotic diuresis produces polyuria, dehydration, an increase in dehydration, an increase in osmolality, and compensatory osmolality, and compensatory polydipsia polydipsia

DMDM

Pyogenic skin infection are most Pyogenic skin infection are most uncommon as a presenting uncommon as a presenting complaint, although vaginitis in complaint, although vaginitis in teenage girls may be the presenting teenage girls may be the presenting featurefeature

Clinical presentationClinical presentation

About 30% of patients initially present About 30% of patients initially present with frank diabetic ketoacidosis:with frank diabetic ketoacidosis:

Air hungerAir hungerKussmaul’s respirationKussmaul’s respirationAcetone on the breathAcetone on the breathObtundation of consciousness or comaObtundation of consciousness or comaVomitingVomitingDehydrationDehydration

HyperglycemiaHyperglycemia

HyperglycemiaHyperglycemia

Clinical presentationClinical presentation

PolyuriaPolyuria PolydipsiaPolydipsia PolyphagiaPolyphagia Weight lossWeight loss LethargyLethargy weaknessweaknessThese symptoms may be present for These symptoms may be present for

days to weeksdays to weeks

Particularities DM in infantsParticularities DM in infants

Lability of the Lability of the water & mineral water & mineral metabolismmetabolism

Stopping or loss Stopping or loss body weightbody weight

Appetite increase Appetite increase or normalor normal

Thirst, active Thirst, active suckingsucking

Particularities DM in infantsParticularities DM in infants

Starch napkins or Starch napkins or sticky stains due to sticky stains due to glucosuriaglucosuria

Dry skin, Dry skin, ↓ ↓ turgor, turgor, skin infectionskin infection

2 types of DM manifestation in 2 types of DM manifestation in infantsinfants

First – acute onset, severe First – acute onset, severe dehydration, intoxication, vomiting, dehydration, intoxication, vomiting, coma as a toxico-infection shockcoma as a toxico-infection shock

Second – dystrophy develops Second – dystrophy develops gradually, infection diseases connectgradually, infection diseases connect

Ketonuria is absent to 4 mo old due Ketonuria is absent to 4 mo old due to liver immaturityto liver immaturity

Diagnosis of DM Diagnosis of DM N.B!N.B!

Clinical presentation & paraclinic: Clinical presentation & paraclinic: hyperglicemia, glucosuria, ketonuriahyperglicemia, glucosuria, ketonuria

Additional: Additional: ↓ ↓ or absents of C-peptideor absents of C-peptide ↑ ↑ glicolized Hb (glicolized Hb (HbAic)HbAic) ↑ ↑ fructosaminefructosamine presents of the antibodies to presents of the antibodies to ßß cells, cells,

Ins and to differens Ins and to differens glutamatdecarboxilase isoformesglutamatdecarboxilase isoformes

Criteria of DM compensationCriteria of DM compensation

The aim of treatment –”QULITY OF The aim of treatment –”QULITY OF LIFE”LIFE”

The adequate growth & The adequate growth & development of childdevelopment of child

Active social position in life & Active social position in life & societysociety

Decreasing acute complication Decreasing acute complication and prolong late complications of and prolong late complications of DMDM

Normal life durationNormal life duration

Criteria of DM compensation Criteria of DM compensation (c’d) in childhood(c’d) in childhood

Glucose level fasting 4-8 mmol/LGlucose level fasting 4-8 mmol/L Glucose after feeding 10-11mmol/L Glucose after feeding 10-11mmol/L

(3.3-8.3 mmol/L – less than renal (3.3-8.3 mmol/L – less than renal threshold)threshold)

Night Glucose level 6-8 mmol/LNight Glucose level 6-8 mmol/L Episodes of Hypoglycemia are absent Episodes of Hypoglycemia are absent

Glucose absent in urineGlucose absent in urine

Criteria of DM compensation Criteria of DM compensation (c’d)(c’d)

Normal lipid, protein and Normal lipid, protein and mineral metabolism mineral metabolism

HbAic, % - 5-7 HbAic, % - 5-7 Cholesterol mmol/L -< 5.2Cholesterol mmol/L -< 5.2 Triglicerids mmol/L - < 1.7Triglicerids mmol/L - < 1.7

Differential DiagnosisDifferential Diagnosis

Diabetes InsipidusDiabetes Insipidus AppendicitisAppendicitis Fancony syndromeFancony syndrome Diabetes Mellitus type IIDiabetes Mellitus type II

Factors influencing Factors influencing vasopressing secretion vasopressing secretion INCREASED SECRETIONINCREASED SECRETION

HypovolemiaHypovolemia HyperosmolalityHyperosmolality Upright positionUpright position Central hyperthermiaCentral hyperthermia Stress and anxietyStress and anxiety Cerebral disease Cerebral disease Chest diseaseChest disease MalignanciesMalignancies Drugs (Carbamazepine, clofibrate Nicotine, Drugs (Carbamazepine, clofibrate Nicotine,

angiotensin II Cholinergic drugs, Morphine, angiotensin II Cholinergic drugs, Morphine, barbiturates)barbiturates)

Factors influencing Factors influencing vasopressing secretion vasopressing secretion DECREASED SECRETIONDECREASED SECRETION

HypervolemiaHypervolemia HyperosmolalityHyperosmolality Recumbent positionRecumbent position Central hyperthermiaCentral hyperthermia Diabetes insipidusDiabetes insipidus Drugs & Alcohol (Dilantin, Drugs & Alcohol (Dilantin,

Anticholinergic agents) Anticholinergic agents)

POLYURIC CONDITIONS POLYURIC CONDITIONS MIMICKING VASOPRESSIN MIMICKING VASOPRESSIN

DEFICIENCYDEFICIENCY

Physiologic suppression of Physiologic suppression of vasopressin secretionvasopressin secretion

Psychogenic polydipsiaPsychogenic polydipsia Organic polydipsia (hypothalamic Organic polydipsia (hypothalamic

disease)disease) Drug induced polydipsia Drug induced polydipsia

(thioridazine, tricyclics)(thioridazine, tricyclics)

POLYURIC CONDITIONS POLYURIC CONDITIONS MIMICKING VASOPRESSIN MIMICKING VASOPRESSIN

DEFICIENCYDEFICIENCY Reduced renal responsiveness to vasopressinReduced renal responsiveness to vasopressin Genetic: nephrogenic diabetes insipidus medullary Genetic: nephrogenic diabetes insipidus medullary

cystic diseasecystic disease PharmacologicPharmacologic:: lithium, demeclocycline, penthrane, lithium, demeclocycline, penthrane,

diureticsdiuretics Osmotic diuresisOsmotic diuresis:: diabetes mellitus reduced diabetes mellitus reduced

nephron populationnephron population Electrolyte disturbanceElectrolyte disturbance:: hypercalcemia hypercalcemia

hypokalemiahypokalemia Renal diseaseRenal disease::postobstructive diuresis, renal postobstructive diuresis, renal

tubular acidosis pyelonephritis, papillary necrosis, tubular acidosis pyelonephritis, papillary necrosis, sickle cell diseasesickle cell disease

Hemodynamic: hyperthyroidismHemodynamic: hyperthyroidism

Diabetic ketoacidosisDiabetic ketoacidosis

Hyperglycemia Hyperglycemia KetonemiaKetonemia Acidosis (pH≤7.3 & bicarbonate less Acidosis (pH≤7.3 & bicarbonate less

than 15 mEq/L)than 15 mEq/L) GlucosuriaGlucosuria KetonuriaKetonuria

Complications of DM (acute)Complications of DM (acute)

Ketoacidosis, ketoacidotic comaKetoacidosis, ketoacidotic coma DehydrationDehydration Nonketotic hyperosmolar comaNonketotic hyperosmolar coma Hypoglicemia, hypoglicemic comaHypoglicemia, hypoglicemic coma Lactoacidotic comaLactoacidotic coma

Complications of DM Complications of DM

Somogy phenomenonSomogy phenomenon Dawn phenomenonDawn phenomenon Brittle DiabetesBrittle Diabetes

Complications of DM (long-Complications of DM (long-term)term)

Diabetic retinopathyDiabetic retinopathy Diabetic Diabetic

nephropathynephropathy Angiophathy of Angiophathy of

lower extremitieslower extremities Diabetic neuropathy Diabetic neuropathy

(periferal, central, (periferal, central, autonomic)autonomic)

Complications of DM (long-Complications of DM (long-term)term)

Mauriac syndrome, Nobecur Mauriac syndrome, Nobecur syndromesyndrome

Syndrome of limited joint mobility Syndrome of limited joint mobility (hairopathy)(hairopathy)

Skin pathology (lipoid necrobiosis, Skin pathology (lipoid necrobiosis, lipodystrophy, paronichia and etc)lipodystrophy, paronichia and etc)

lipoid necrosis'slipoid necrosis's

lipoid necrobiosislipoid necrobiosis

lipoid necrobiosislipoid necrobiosis

Diabetes Mellitus in ChildrenDiabetes Mellitus in Children