DM in children

Diabetes Mellitus in Children

It is common chronic metabolic disorder characterised by hyperglycaemia

Major classification into:

Type 1 DM, Deficiency of insulin secretion due to pancreatic B-cell damage.
Type 2 DM, Insulin resistance at level of skeletal muscle, liver, adipose tissue with various degree of B-cell impairment.

Type 1 DM

It is the commonest endocrine disorder in childhood and adolescence with important consequence of physical and emotional development with absolute requirement of daily exogenous insulin, need to monitor glucose and pay attention to dietary intake.

Type 1 DM

Morbidity is due to long term macro vascular and micro vascular complication as ischaemic heart disease, peripheral arterial disease and neuropathy, retinopathy and nephropathy due to metabolic disturbance following hyperglycaemia.
Autoimmune mechanism are factors in the genesis of Type 1 DM.

Epidemiology of Type 1DM

It account for 10% of all diabetes and there are 15 million peoples in the world having Type 1DM.
It is not limited to the age ,new cases continue to appear in adult life, and 50% of them present in adults.
There are differences among race and countries


Epidemiology
It is highest in Finland 34/100,000 and lowest in Pakistan 0.7/100,000
There are annual increase in incidence in western countries 2.5% and more rapid in central and eastern Europe.
The rate is increasing more in younger children.
Girls and boys are equally affected but female more in low risk population.

Epidemiology

2 Peaks ,one at age of 5-7 years and at time of puberty, the first correspond to infectious agents with beginning of the school, the second correspond to pubertal growth hormone secretion which antagonise insulin.
A growing number between 1-3 years of age
Especially at high risk population

Epidemiology

The migrants from low risk countries to high risk countries will have the incidence risk of that high risk.
No relation found to socio economic status.

Aetiology

Genetics;
The prevalence in general population
In 0.4%.,but in sibling is 6%.
The risk is increased if parents are affected
7% if the father is affected, 2% if the mother is affected.
The risk of parents if the child is affected is 3%


Gene discovered
Autoimmune polyendocrinopathy syndrome type 1(APS1);mutation of AIRE,abnormality in expression of peripheral gene within the thymus,Type1DM appear in 18% of cases.
Immune dysfunction polyendocrinopathy-Enteropathy -X linked (IPEX) ,mutation of FOXP3 which regulate the function of T-cell with result of sever over whelming autoimmunity and DM appear as early as 2 days of age

Genetics

The concordance in monozygotic twins is 30-65%, but in dizygotic twin is 6-10%.
85% of childhood Type1DM have no family history of Type 1DM.

Genetics

MHC/HLA encoded susceptibility to Type1DM
Are I II III IV, II is the most frequently associated with the risk, great variations are present, it is linked to DR3&DR4 alleles with linkage to DQ region2/8 ,the risk is 50% if one sibling haplotype and increase to 80% when siblings share both HLA haplotype identical by descent.

Genetics

Aspartate at position 57 in DQB1 has a role

DQB1 O3O2 high risk for Type 1DM .

DQB1 0301 (protective) Low risk.

Genetics

The Gene responsible for Type 1DM is the major histocompatibility complex(MHC/HLA)
On chromosome 6 promoter region S insulin gene on chromosome 11.
Other studies includes Insulin Protein Tyrosine Phosphatase Non receptor 22 and 2(PTPN22),(PTPN2)
Interleukin IL-2,Cytoxic lymphocyte antigen 4,lectin like gene, but their contribution are low except PTPN22


Enviromental
Discordant in monozygotic twin
Variations in rural and urban of same ethnic origin.
Change with migration
Increase in last 2decades in all population.
seasonality

Enviromental

Viral, congenital rubella syndrome,B-cell immunity in 70% and T1DM in 40% the time lag between infection and disease may be as high as 20 years.
Enterovirus,increase in enterovirus RNA in prenatal blood sample in children who subsquently develop TIDM
Mump,increase in incidence of T1DM after

Enviromental

Epidemics of mump.
Immunization vaccine against mump and pertusis decrease T1DM
Hygiene hypothesis, lack of exposure to infection increase risk to development of autoimmune diseases including T1DM
The incidence of autoimmunity varies with IgE
Antibody involved in parasitic infection

Enviromental

Diet, breast feeding decrease the risk to T1DM
Psychological stressful situation whether aggravating or trigger for autoimmunity to develop T1DM.
Role of overweight and accelerated hypothesis with development of insulin resistance, which occur in T2DM.
It is not known if it is distinct entity or both T1DMand T2DM have the same origin.


Pathogenesis and natural history
1-Initation of autoimmunity ,which starts before 2years of age, with appearance of Insulin associated antibody( IAA), glutamic acid decarboxylase (GAD65) and tyrosine phosphatase insulinoma associated 2(1A-2).
2-preclinical of autoimmunity with progressive
Loss of B-cell function
3-onset of clinical disease

Natural history

4-Transeint remission because of presence of some viable cells that continue to secrete insulin and the need for exogenous insulin is decreased, it is called honey moon period
5-Established disease that has to depend absolutely on exogenous insulin.
6-Development of complication depending on degree of the metabolic control.

Prevention

Primary:
delay in introduction of cows milk and cereals with the increase duration of breast feeding.
Supplementation of Vit D, Omega 3 fatty acid and cod liver oil during pregnancy hints some benefit but not conclusively proven.
Anti GAD alum and anti CD3 antibodies to subjects at risk.

prevention

Secondary: during honney moon period
Cytoxic drugs like Cyclosporin that act on Interferon tumor necrosis factor but because of site effects it has been abonded.
CD3 antibodies ,it has proven, but because of site effect of flue illness and Epstein virus infection it is not used.
Glucagon like peptide agonists e. g Exantide alone or with combination with immunomodulation drug to increase B cell mass.


Pathphysiology
In TIDM a permanent fasting or low insulin status resulting in decrease of glucose and fat uptake by muscle resulting in hyperglycaemia and glycosuria resulting in osmolar dehydration with resultant hyper secretion of insulin antagonists like epinephrine, cortisol , glucagon and growth hormone accelerate lipolysis, decrease lipid synthesis, increases plasma lipid ,cholesterol, triglyceride and free fatty acids.

pathophysiology

The hormonal interplay of insulin deficiency and glucagon excess shunt the free fatty acids into ketone bodies, B- hydroxybutyrate and acetoacetate exceed the peripheral utilization and renal excretion results in metabolic acidosis DKA, compensatory deep rapid breathing in an attempt to excrete CO2 (kussmaul breathing) .

pathophysiology

Acetone is responsible for fruity odour of breath ,is formed by non enzymatic conversion of acet acetate.
Ketone is excreted in urine with cations, thus increase lose of water and electrolyte with progress of dehydration ,acidosis , hyperosmolarity, diminished cerebral oxygen utilization, impaired consciousness and coma

Clinical manfestations

It starts with polyuria and nocturia and when the hyperglycaemia become persistent the nocturia persists and polydypsia with lose of calories in urine results in polyphagia and lose of weight in spite of polyphagia.
With persistent low insulin ,formation of ketone bodies causing nausea , abdominal discomfort and dehydration ,kausmaul breathing with disturbed consiousiness

pathophysiology

In young children the manifestations are more rapid in term of dehydration and acidosis but in adolescents the condition is more prolonged and starvation is more prolonged and cause lose of weight which may be also to dehydration prior to diagnosis, this is usually exacerbated by preceding infection and counter regulating hormone due to stressful condition .

Diagnosis

It is usually straight forward ,the symptoms are non specific, presence of polyuria in spite of dehydration ,flue illness.
Hyperglycaemia, glycosuria and ketonuria are easily diagnosed.
Blood glucose fasting or non fasting above 200mg/dl (11.1Mmol/L) with or without ketosis,if ketone are present look for electrolyte abnormality even if dehydration is mild,


HBA1C determination to estimate duration of DM.
If non obese child look for other autoimmune disease like celiac and thyroid disease by doing tissue transglutaminase antibodies IgA and IgG and anti thyroid peroxidase and thyroglobulin antibodies,TSH and free T4 few weeks after stabilization of the condition.

For stress hyperglycaemia ,post prandial and glucose tolerance tests are not needed.

DIABETIC KETOACIDOSIS
It occur in 20-40% of cases of variable severity
Depending on the degree of depth of breathing, amount of ketonuria, anion gap, the decrease of PH and bicarbonate, the serum osmolality indicating hypertonic dehydration.

Diabetic ketoacidosis

Normal mild moderate sever
CO2 20-28 16-20 10-15 <10
Meq/l
PH 7.35-7.45 7.25-7.35 7.15-7.25 <7.15
Clinical :No chang e fatique kausmal kuasmal
oreinted depressed
sleepy sensorium
coma

Treatment

Objective in cases with no DKA:
:to maintain a balance between tight glucose with no hypoglycaemia,
To eliminate polyuria and nocturia
To prevent DKA
To permit normal growth and development
With minimum effect on life style


Dose
Mid puberty about 1 iu/kg/day
Late puberty about 1.2 iu/kg/day
In newly diagnosed cases 60-70%
Of replaced dose based on pubertal status
The optimal dose can be determined empirically with self monitoring and insulin adjustment by the diabetic team.

treatment

Start with initiation of Insulin
Extensive teaching of child and caretaker
Reestablilisation of life routine
Start therapy in outpatient with complete team of paediatric endocrinologist, diabetic nurse and educator,dietition,social worker otherwise it should be in hospital

Insulin therapy-Dose

Insulin need is higher in puberty and in those having greater deficit to restore their glycogen,protein,fat.
Most children have residual B- cell function (honey moon period) when the need of exogenous insulin is declined , It resolve within few months and reflected by steady increase in need of insulin.
Children with long standing DM and no insulin reserve needs:
Prepubertal about 0.7iu/kg/day

Type of Insulin and regimen

Insulin analogue is nearer to the physiological insulin,that is basal- bolus regimen(Intensive-MDI),it decrease postprandial and mid meal hypoglycaemia.
Basal slow onset –long duration between meals and bolus of rapid onset insulin for each meal.
The difference between analogue and preanolque is that the later form hexamer dissociate to monomer which needs time to absorb and has wider peak and longer effect


Insulin dose , type and regimen
e,.g 6yrs old boy weigh 20kg needs about 0,7u/kg/24h=14u/24h----7u as basal as Glargin and 7u as bolus before meals 2u of lispro or aspart .,substract 1u if the blood sugar below target and add 0.75u for each 100mg above target(near to 0.5u),bolus but not basal dose modified according to CHO intake.
For tight control you can add in 50mg/dl increment.

Insulin type and regimen

So liable for hypoglycaemia between meals , postprandial and nocturnal.
so the injection needs time before meal and snacks between the meals in addition to the timing of the lente or NPH superimpose on the peak of regular insulin

Subcutaneous insulin dosing

AGE Target total basal bolus
glucose daily % of total unit added
mg/dl u/kg/d dose 100mg/dl 15g
0-5 100-200 0.6-0.7 25-30 0.5 0.5
5-12 80-150 0.7-1.0 40-50 0.75 0.75
12-18 80-130 1.0-1.2 40-50 1.0-2.0 1-2.0

Regimen of insulin

Tight control increase risk of hypoglycaemia to 3 folds ,it is less with analog but it does not eliminate it.
Some children don’t wont 4 injections ,you can give 3 injections regimen of NPH and rapid acting insulin at brekfast,rapid acting at supper and NPH at bed time, but this has poor coverage at lunch and early morning and increase risk of hypoglycaemia at midmorning and early night.

DKA
3 essential changes following the sever insulopenia and lack of effective insulin action:
1-excessive glucose production , reduced glucose utilization leads to osmotic diuresis with lose of water and electrolyte results in activation of renin and angiotensin axis with accelerated K lose.
If glucose elevation and dehydration are sever for several hours potentiate cerebral oedema.


DKA
2-Increases catabolic process result in cellular lose of Na K Phosphate.
3-Increase of FFA from peripheral fat store ,supply substrate for hepatic ketoacid production then buffer system depleted and metabolic acidosis ensues.

Treatment of DKA

Addressed to;
1-Insulopenia 2-Physiological disruption
And taking care of :
A-hypoglycaemia B- Hypokalaemia C-cerebral oedema.
Need for close monitor of patient and any protocol used with caution.

Treatment of DKA

Insulin
Must be given at the beginning to:
Accelerate the entrance of glucose into cells and decrease hepatic production of glucose
And halt movement of FFA from periphery to
Liver
Note: Bolus dose does not speed recovery but increase danger of hypoKalemia and cerebral oedema

Treatment of DKA

So Insulin infusion without bolus at rate of 0.1 u/kg/hr=approximate max insulin output during OGTT.
Rehydration decrease glucose level by improving renal perfusion and enhance renal excretion
So Insulin and IVF cause rapid decline of blood glucose and once blood glucose decrease to 180 mg/dl, osmotic diuresis stop and rehydration


Protocol of DKA
Need for flow chart to monitor input and output,neurological assessment for cerebral edema and mannitol should be ready1g/kg/iv.
Airway-breathing O2
Nothing per oral.+NGT
Iv infusion in first hr should be quick and can be repeated and need to deducted from total rehydrated fluid

Protocol of DKA

1ST HR; 10-20M/KG/IV of 0.9%NS
Insulin 0.05-0.1 iu/kg/hr
2nd hr, 0.45%NS plus insulin drip on same conc
until resolution of DKA; 20mEq Kphosphate and 20 mEq Kacetate plus 5% glucose if blood sugar down to >250mg/dl or 14mmol/l
IV Rate=85ml/kg +maintaince-bolus /23h
Or deficit +48hrs maintaince80ml<1y,70m1-5,60ml6-9y,50ml10-14y,35ml>15y

Protocol of DKA

Repair of rehydration occur before correction of acidosis ,t.f insulin infusion continues to control fatty release after normal glucose level has reached.
And 5%glucose addition to prevent hypoglycaemia after bl.glucose has reached 250mg/dl

Protocol of DKA

If K<3mEq increase K to 0.5-1mEq/kg or 80mEq/l.
Oral intake plus subcutaneous can be started when no emesis and when CO2>16mEq/l and normal electrolyte.


Treatment of DKA
Infusion rate can be lowered once hyperglycamia has resolved.
Repair of fluid deficit tempered by potential risk of cerebral oedema, so appraoch to hyperosmalr dehydration with caution.

Eosm=2xNammol/l(uncorrected)+glucose mmol/l=actual tonicity of body fluid.

It is usually high at start ,it should be declined steadily to normal otherwise rapid or slow potentiate cerebral oedema indicating an excess of free water entering vascular space .
T.f oral fluid not allowed but ice chips as minimal oral intake
Until rehydration is well progressed and no more shift of electrolyte

Treatment of DKA

Clinical signs of dehydration is not well seen but tachycardia and delayed capillary filling ,decrease temperature, and orthostatic blood pressure changes ,in this status the child are more dehydrated than norm tonic dehydration. In sever DKA 30-36 hours are needed or even 48 hrs while mild just 24hrs is needed to start oral fluid.

Treatment of DKA

Na initially low (FAULSE)or normal
Corrected Na=Na +glucose mg/dl/-100x1.6/100
Corrected Na=Na+glucose mmol/l-5.6x1.6/5.6
The result added to 100
Na increase by 1.6 for decline of 100mg of blood glucose.if the corrected above 150meq/l slower fuid replacement.


With prolonged illness and sever DKA lose of Na,K and Phosphate that need several days to restore.
Decrease Na indicate excess free water accumulation and cerebral oedema

And increase risk of myocardial dysfunction with increase acidosis and shock

Kcl increase to 80meq/l or oral kcl and rarely IV infusion of insulin need to be stopped
Phosphate deficit
Contribute to symptoms of DKA ,such as muscular weakness. a deficit has not been shown to comprise 02 delivery via 2,3,DPG

K
Either normal or high due to movement of K from intracellular space into serum due to buffer and catabolism.
It is reversed by therapy and K back into cell with rehydration and increase renal renal flow ,K excreted in urine in elevated aldosterone state results in hypokalaemia (flattening of T wave and prolonged QRS).Muscle weakness

Excess of cl induce acidosis so k can be given as phosphate or acetate

Blood urea increase due to prerenal dehydration which goes back to normal on rehydration
Crisis falsely increases owing to interference with ketone ,but increased urea and creatinine are not indication to withhold K therapy

Serum amylase increase due to pancreatitis

Ketoacid accumulation continues, this need continuation of insulin infusion at 0.02-0.05u/kg/hr to stop release of peripheral FFA
And is declined when blood glucose decline to 150mg/dl and addition glucose to fluid, ketone formation is decreased ,as well buffer of HCO3 in renal tubule and metabolism of ketone.

PH and HCO3 are increased , KUASMAL breathing and abdominal pain abated without addition of NaHCO3.
Persistance of acidosis indicate;
1- infection
2-inadquate fluid therapy
3-lactic acidosis


Persistence of + ve Ketone after resolution of ketacidosis
It is due to conversion of B-hydroxybuturate to acetacetate which stay positive on Na nitroprusside test

Question, Why you don’t treat every metabolic acidosis with alkali (sodium bicarbonate infusion)?

Nutritional requirement

Objective; to meet the normal caloric required according to age sex taking into consideration
Of cultural recipes and child favourites, and as
Normal the distribution of calories are;
CHO 55%,FAT30% PROTEIN 15% and according to meals as 20% for each of breakfast, dinner and 30% supper with 10% mid-afternoon and prebedtime snacks.
With restriction of refined sugar, but it is needed when there is risk of hypoglycaemia(exercise) and in birthday parties (add insulin)

nutrition

CHO –Use the exchange of CHO of 15gm,and Insulin /CHO count is more flexible and improve quality of life.
Protein;12-20% of energy otherwise high protein increase risk for nephropathy
Fat; polunsaturated/saturated=1.2/1(veg oil/animal fat).limit egg yolk to decrease LDL and to decrease atheroscelorosis

Less than 10% of calories from animal fat

And ---------10%polyunsaturated fat
Remaining -------monounsaturated fat
Diet rich in fiber decrease absorption of sucrose and improve the control.
Sweetening agents like saccharine ,its association with bladder cancer is not yet confirmed.


Aspartame should not be used because of its implication in diabetic complication through polyol pathway.
Glycaemic index is under investigation in children.
Education about eating habits is superior to prevent eating disorder and obesity which occur in adolescent girls and dealt in sensitive manner.
How to prevent hypoglycaemia during exercise, to prevent ketoacidosis during heavy exercise.
Dietary revision every 3months.

Self-Monitoring blood glucose

SMBG, Self monitoring blood glucose;
Strip impregnated with glucose oxidase that permit measurement of blood glucose from drop of blood.
Measurements of Premeals, prebedtime and early morning. And including exercise, dietary change ,illnesses and hypoglycaemic events.

SMBG

If FBG is high-increase long acting by 10-15%+additional fast dose for bedtime.
If presupper is high increase fast dose of dinner at noon by10-15%.
If prebed time is high increase the presupper fast dose to 10-15%.
If hypoglycaemia has occurred the fast dose decreased to corresponding times similarly.

EXERCISE

No form of exercise is forbidden;
major complications are: hypoglycaemia and ketoacidosis because of counter regulatory hormones.
In anticipated exercise increase portion of CHO and decrease and decrease dose of total insulin dose by 10-15%,in prolonged exercise decrease dose by 50%.
Watch for hypoglycaemia several hours after exercise.


CGMS
Subcutaneous sensor expressing blood glucose up to 72 hours and put between 40-400m/dl
Real time CGM –during night for discovering nocturnal hypoglycaemia.
HBA1C;
Non enzymatic attachment of glucose to haemoglobin , it is expressed as fraction of HB and it reflect the amount of blood glucose in last 2-3months.it increase in thalassemia and decrease in sickle cell anaemia

HBA1C is expressed as % it indicate the metabolic control:

<6% --------normal
6-7.9%----good control
8-9.9%----fair control
>10%-----poor control

Improve glycaemic control

DCCT(Diabetes control complication trial)
Has shown the relation of long term diabetic complication with high HBA1C, and intensive therapy reduce micro vascular complication by 47%,but with increase in frequency of hypoglycaemia and putting more weight in adolescents.
Other trial of EPIC(Epidmiology Diabetes Intervention Complication) demonstrate reduction cvs by 42%,strokes, non fatal heart attacks and deaths by 57%.

Hypoglycaemia

Young children are at risk for sever hypoglycaemia and its complication on cognitive function . It follows omitted or delayed meals and exercise .
Mild hypo- occurs weekly ,moderate occurs as few per year and sever occurs once every few years. It is dangerous if the child has autonomic dysfunction and lose of epinephrine response to hypoglycaemia. So occurrence of hypoglycaemia without awarness .


Recurrent hypoglycaemia with tight control is increased ,with deficiency of counter-regulatory response leads to hypoglycaemia unawareness and reduced ability to restore glycaemia(hypoglycaemia associated autonomic failure).Avoidance of hypoglycaemia to allow recovery from unawareness syndrome

Somogyi and Dawnphenomenan

Somogyi ; rebound hyperglycaemia following late night and early morning hypoglycaemia and exaggerated by couter-regulatary H. It is unlikely to remain hypo without rebound.CGM discover it and clarify the ambiguity of increase bl. glucose on morning.
Dawn due to overnight GH secretion which occur in non diabetics , blood glucose increase on morning due also to low basal insulin levels of NPH and Lente .

Brittle Diabetes

It is usually in adolescents, wide flucutation in blood gucose with recurent DKA .They have normal insulin response at hospital.
This is due to psychological or psychiatric problem including eating disorder, dysfunction family dynamics.
Treatment; hospitalization to elevate enviromental factors aggressive psycological or psychiatric evaluation.

Non adherence and non compliance

Like deliberate overdose, omission of of insulin, excess of intake ,refusal of self monitoring results in frequent hospitalization due to DKA ,Fear of self injection ,NOT rotating the sites due to less pain causing lipid hypertrophy and poor absorption and poor metabolic control.

It occur when there is family conflict ,denial ,anxiety overprotective parents and when there is behaviour problem in the child.
Or when parents are concerned about other sibling, about complications about pregnancy.

Behaviour /psychological upset/eating disorder

No specific personality disorder or psychopathology is characteristic of diabetic children. Similar feeling found in families of children with chronic diseases.
Feeling of anxiety and guilt in parents and denial neglect in children, particularly during
Rub bilious adolescent teenage years, with family conflict cause poor adherence to metabolic control. The way that child manage during stressful factor, most try to avoid stress , but the ideal is to manage the stress in mature manner.



Approach to such cases
Empathetic counselling ,built the feeling of normality, and of being reproductive in the society.
Peer discussion, education about diabetes, summer camp.resedential treatment.
20-26% of females has depression as normal

Sharing responsibilities result in better psychological health ,good self behaviour and good metabolic control. In cases of psychological and behaviour abnormality and eating disorder like anorexia nervosa or bulimia refer to psychiatrist
Cognitive function; early onset and long duration of Diabetes adversely affect school performance.
It affect learning ,memory skills (verbal and visual) with attention, executive function skills.

During infection

During infection counter regulatory H increase risk of acidosis, dehydration and anorexia decrease blood glucose and treatment accordingly.
During surgery ,disrupt metabolic control because of stress H and surgery itself increase glucose and ketosis or calories decreases and hypoglycaemia.so need to maintain blood glucose with no ketosis

Long term complication

Microvascular complications:
Retinopathy, is leading cause of blindness ,it increase after 15 years duration in at least 5% of age under 19 years. It is due to activation of POLYOL pathway.
NPDR(microaneurysm,dot and blot hamorrahge,hard andsoft exudate) and PDR (fibrosis,profileration and retinal detachment )
Macular edema-photocoagulation

Diabetic nephropathy

Leading cause of end stage renal disease in 20-30% of T1DM,dueto glycation of tissue protein resulting in GBM thickening-albumin excretion –glomerular hyperfilteration –decrease in renal functions progressive proteinuria and hypertension.
Treatment transplataton,diaylasis


Diabetic nephropathy
Both peripheral and autonomic can be involved.
Adolescents can show early evidence of neuropathy due to hyperglycaemia and decease insulin in peripheral nerves.
The polyol pathway nonezymatic glycationand disturbance of myoinositol metabolism in peripheral nerve

Diabetic neuropathy

Abnormal thermal perception and subclinical
Impairment of motor nerve.
Treatment, improve metabolic control
Aldose reductase inhibbitor
Lipoic acid(antioxidant)
anticovalsants

Screening guidelines

DR,Commence after 5y duration in prpubertal and 2y in pubertal,every 1-2y,by doing fundal photography,and florucin angiography and mydiatric opthalmoscopy.
Intervention:improve glycemic control and laser therapy

Screening guidelines

DN,commence 5y in prepubertal and 2y in pubertal, and annually are screened
Tested by overnight urine excretion of albumin, and 24 hr excretion of urinary Alb/Cr ratio.
Intervention; improve glycaemic control ,blood pressure control and ACE inhibitor.


Screening guidelines
D Neuropathy it is unclear when to commence and how often to do screening ,but physical ex
For n conduction,thermal and vibration threshold,pupillometery and CV reflexes
Intervention; improve glycemic control.

screening

Macrovascular ;commence after age 2 y and every 5y by measurements of serum lipids ,blood pressure
Intervention; statins and blood pressure control.
Thyroid disease, commence at diagnosis and every 2-3y by measurement of TSH ,THYROID PEROXIDASE antibody.
Intervention-Thyroxine

Celiac disease commence at diagnosis and every 2-3y by tissue transglutaminase and antiendomysial AB ,and antigliadin.
Interventon-gluten free diet

Other long term complications

Mauriac syndrome consists of dwarfism, ostopenia ,limited joint mobility waxy skin due to underinsulinization
Proximal musculae westing, hepatomegaly due to fat and glycogen infilteration
And development of micrvascular complication before age of 15y.

Prognosis

Life expectancy is 10y shorter, they achieve normal adult height but less than their genetic potential and delayed puberty may occur.
Segmental Pancreatic transplantation may prolong life and improve the complication but danger of rejection and complication of immunosuppression and recurrence of the disease.
Islet cell transplantation strategy is challenging because of rejection and complication


References
Nelson Textbook of Paediatrics 19TH edition

Quiz

You need to care of what during treatment of DKA?