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Back to List
Diabetes Mellitus 

INTRODUCTION
Background: Diabetes mellitus (DM) is a chronic metabolic disorder caused by an absolute or relative deficiency of insulin, an anabolic hormone. Insulin is produced in the pancreas by the beta cells of the islets of Langerhans. Absence, destruction, or loss of these cells causes an absolute deficiency of insulin, leading to type 1 diabetes (insulin-dependent diabetes mellitus [IDDM]). Most children with diabetes have IDDM and a lifetime dependence on exogenous insulin.

Type 2 diabetes (non–insulin-dependent diabetes mellitus [NIDDM]) is a heterogeneous disorder. Patients with NIDDM have insulin resistance, and their beta cells lack the ability to overcome this resistance. Although this form of diabetes previously was uncommon in children, 20% or more of new patients with diabetes in childhood and adolescence now have NIDDM, a change associated with increased rates of obesity.

This chapter addresses only IDDM.

Pathophysiology: Insulin is essential to process carbohydrate, fat, and protein. Insulin reduces blood glucose levels by allowing glucose to enter muscle cells and fat cells and by stimulating the conversion of glucose to glycogen (glycogenesis) as a carbohydrate store. Insulin also inhibits the release of stored glucose from liver glycogen (glycogenolysis) and slows the breakdown of fat to triglycerides, free fatty acids, and ketones. Additionally, insulin slows the breakdown of protein for glucose production (gluconeogenesis).

Hyperglycemia (ie, random blood glucose concentration more than 200 mg/dL or 11 mmol/L) results when insulin deficiency leads to uninhibited gluconeogenesis and prevents the use and storage of circulating glucose. The kidneys cannot reabsorb the excess glucose load, causing glycosuria, osmotic diuresis, thirst, and dehydration. Increased fat and protein breakdown leads to ketone production and weight loss. Without insulin, a child with IDDM wastes away and eventually dies from diabetic ketoacidosis (DKA).

Frequency:
 

  • In the US: Overall incidence is approximately 15 cases per 100,000 individuals annually and probably increasing. An estimated 3 children out of 1000 develop IDDM by age 20 years.
  • Internationally: DM exhibits wide geographic variation in incidence and prevalence. Annual incidence varies from 0.61 cases per 100,000 persons in China, to 34.4 cases per 100,000 in Sardinia, and more than 40 cases per 100,000 in Finland. Substantial variations exist between nearby countries with differing lifestyles, such as Estonia and Finland, and between genetically similar populations such as those in Iceland and Norway. These variations strongly support the importance of environmental factors in the development of IDDM. Many countries report that incidence rates have doubled in the last 20 years. Incidence appears to increase with distance from the equator.

Mortality/Morbidity: Information on mortality rates is difficult to ascertain without complete national registers of childhood diabetes, although age-specific mortality probably is double that of the general population. Particularly at risk are children aged 1-4 years who may die with DKA at the time of diagnosis. Adolescents also are a high-risk group. Most deaths result from delayed diagnosis or neglected treatment and subsequent cerebral edema during treatment for DKA, although untreated hypoglycemia also causes some deaths.

IDDM complications are comprised of 3 major categories: acute complications, long-term complications, and complications caused by associated autoimmune diseases.

  • Acute complications reflect the difficulties of maintaining a balance between insulin therapy, dietary intake, and exercise. Acute complications include hypoglycemia, hyperglycemia, and DKA.
  • Long-term complications arise from the damaging effects of prolonged hyperglycemia and other metabolic consequences of insulin deficiency on various tissues. While long-term complications are rare in childhood, maintaining good control of diabetes is important to prevent complications from developing in later life. The likelihood of developing complications appears to depend on the interaction of factors such as metabolic control, genetic susceptibility, lifestyle (eg, smoking, diet, exercise), pubertal status, and gender. Long-term complications include the following:

     

    • Retinopathy

       
    • Cataracts

       
    • Hypertension

       
    • Progressive renal failure

       
    • Early coronary artery disease

       
    • Peripheral vascular disease

       
    • Neuropathy, both peripheral and autonomic

       
    • Increased risk of infection
  • Associated autoimmune diseases are common with IDDM, particularly in children who have the human leukocyte antigen DR3 (HLA-DR3). Some conditions may precede development of diabetes; others may develop later. As many as 20% of children with diabetes have thyroid autoantibodies.

Race:

  • Different environmental effects on IDDM development complicate the influence of race, but racial differences clearly exist.
  • Whites have the highest reported incidence of IDDM; Chinese, the lowest.
  • American whites are 1.5 times more likely to develop IDDM than American blacks or Hispanics.

     

  • Current evidence suggests that when immigrants from an area with low incidence move to an area with higher incidence, their IDDM rates tend to increase toward the higher level.

Sex:

  • The influence of gender varies with the overall incidence rates.
  • Males are at greater risk in regions of high incidence, particularly older males, whose incidence rates often show seasonal variation.
  • Females appear to be at a greater risk in low-incidence regions.

Age:

  • Generally, incidence rates increase with age until mid-puberty, then decline after puberty, but IDDM can occur at any age. Onset in the first year of life, though unusual, can occur and must be considered in any infant or toddler, because these children have the greatest risk for mortality if diagnosis is delayed. Their symptoms may include the following:

     

    • Severe monilial diaper rash

       
    • Unexplained malaise

       
    • Increased thirst

       
    • Vomiting and dehydration, with a constantly wet diaper
  • Where prevalence rates are high, a bimodal variation of incidence has been reported that shows a definite peak in early childhood (ie, 4-6 y) and a second, much greater peak of incidence during early puberty (ie, 10-14 y).

CLINICAL
History:

  • The most easily recognized symptoms are secondary to hyperglycemia, glycosuria, and ketoacidosis (KA).
  • Hyperglycemia: Hyperglycemia alone may not cause obvious symptoms, although some children complain of general malaise, headache, and weakness. They also may become ill-tempered. The main symptoms of hyperglycemia are secondary to osmotic diuresis and glycosuria.
  • Glycosuria: This condition leads to increased urinary frequency and volume (eg, polyuria), which is particularly troublesome at night (eg, nocturia) and often leads to enuresis in a previously continent child. These symptoms are easy to overlook in infants because of their naturally high fluid intake and diaper use.
  • Polydipsia: Increased thirst, which may be insatiable, is secondary to the osmotic diuresis causing dehydration.
  • Weight loss: Insulin deficiency leads to uninhibited gluconeogenesis, causing breakdown of protein and fat. Weight loss may be dramatic, even though the child’s appetite usually remains good. Failure to thrive and wasting may be the first symptoms noted in an infant or toddler and may precede frank hyperglycemia.
  • Nonspecific malaise: While this condition may be present before symptoms of hyperglycemia, or as a separate symptom of hyperglycemia, it often is recognized only retrospectively.
  • Symptoms of ketoacidosis
    • Severe dehydration

       

    • Smell of ketones

       

    • Acidotic breathing (ie, Kussmaul respiration), masquerading as respiratory distress

       

    • Abdominal pain

       

    • Vomiting

       

    • Drowsiness and coma
  • Other nonspecific findings
    • Hyperglycemia impairs immunity and renders a child more susceptible to recurrent infection, particularly of the urinary tract, skin, and respiratory tract.
    • Candidiasis may occur, especially in groin and flexural areas.

Physical:

  • Apart from wasting and mild dehydration, children with early diabetes have no specific clinical findings.
  • Physical examination may reveal findings associated with other autoimmune endocrinopathies, which have a higher incidence in children with IDDM (eg, thyroid disease with symptoms of overactivity or underactivity and possibly a palpable goiter).
  • Cataract may be the presenting problem, usually in girls with a long prodrome of mild hyperglycemia.
  • Necrobiosis lipoidica usually, but not exclusively, occurs in people with diabetes. Necrobiosis most often develops on the front of the lower leg as a well-demarcated, red atrophic area. The condition is associated with injury to dermal collagen, granulomatous inflammation, and ulceration. The cause of necrobiosis is unknown, and the condition is difficult to treat.

Causes: Most cases (95%) of IDDM are the result of environmental factors interacting with a genetically susceptible person. This interaction leads to the development of autoimmune disease directed at the insulin-producing cells of the pancreatic islets of Langerhans. These cells are progressively destroyed, with insulin deficiency usually developing after the destruction of 90% of islet cells.

  • Genetic issues
    • Clear evidence exists for a genetic component to IDDM.
    • Monozygotic twins have a 60% lifetime concordance for developing IDDM, although only 30% do so within 10 years after the first twin is diagnosed. In contrast, dizygotic twins have only an 8% risk of concordance, which is similar to the risk between other siblings.
    • The risk of diabetes developing in children with a diabetic mother is 2-3% and 5-6% if the father has IDDM. The risk to children rises to almost 30% if both parents are diabetic.

       

    • HLA class II molecules DR3 and DR4 are associated strongly with IDDM. Over 90% of whites with IDDM express 1 or both of these molecules, compared to 50-60% in the general population.

       

    • Patients expressing DR3 also risk developing other autoimmune endocrinopathies and celiac disease. These patients are more likely to develop diabetes at a later age, to have positive islet cell antibodies, and to appear to have a longer period of residual islet cell function.

       

    • Patients expressing DR4 usually are younger at diagnosis and more likely to have positive insulin antibodies, yet they are unlikely to have other autoimmune endocrinopathies.

       

    • The expression of both DR3 and DR4 carries the greatest risk of IDDM; these patients have characteristics of both the DR3 and DR4 groups.
  • Environmental factors
    • Environmental factors are important because even identical twins have only a 30-60% concordance for IDDM, and because incidence rates vary in genetically similar populations under different living conditions.

       

    • No single factor has been identified, but infections and diet are considered the 2 most likely environmental candidates.
    • Viral infections may be the most important environmental factor in the development of IDDM, probably by initiating or modifying an autoimmune process. Instances have been reported of a direct toxic effect of infection in congenital rubella. A recent survey suggests enteroviral infection during pregnancy carries an increased risk of IDDM in the offspring. Paradoxically, IDDM's incidence is higher in areas where the overall burden of infectious disease is lower.
    • Dietary factors also are relevant. Breastfed infants have a lower risk for IDDM, and a direct relationship exists between per capita cow milk consumption and incidence of diabetes. Some cow milk proteins (eg, bovine serum albumin) have antigenic similarities to an islet cell antigen. Nitrosamines, chemicals found in smoked foods and some water supplies, are known to cause IDDM in animal models; however, no definite link has been made with humans.
  • Chemical causes: Streptozotocin and RH-787, a rat poison, selectively damage islet cells and can cause IDDM.
  • Other causes
    • Congenital absence of the pancreas or islet cells
    • Pancreatectomy
    • IDDM secondary to pancreatic damage (ie, cystic fibrosis, thalassemia major, hemachromatosis, hemolytic uremic syndrome)
    • Wolfram syndrome (diabetes insipidus, DM, optic atrophy, deafness [DIDMOAD])
    • Chromosomal disorders such as Down syndrome, Turner syndrome, Klinefelter syndrome, or Prader-Willi syndrome

Other Problems to be Considered:

Type 2 diabetes (NIDDM)
Psychogenic polydipsia
Nephrogenic diabetes insipidus
High-output renal failure
Transient hyperglycemia with illness and other stress
Steroid therapy
Factitious illness (Munchausen syndrome by proxy)

WORKUP
 Lab Studies:

  • The need for and extent of laboratory studies vary, depending upon the general state of the child's health. For most children, only urine testing for glucose and blood glucose measurement are required for a diabetes diagnosis. Other conditions associated with diabetes require several tests at diagnosis and at later review. (See Diabetic Ketoacidosis for information on laboratory studies needed to manage cases of DKA.)
  • Urine glucose
    • A positive urine glucose test suggests but is not diagnostic for IDDM. Diagnosis must be confirmed by test results showing elevated blood glucose levels.

       

    • Test urine of ambulatory patients for ketones at the time of diagnosis.
  • Urine ketones
    • Ketones in the urine confirm lipolysis and gluconeogenesis, which are normal during periods of starvation.

       

    • With hyperglycemia and heavy glycosuria, ketonuria is a marker of insulin deficiency and potential DKA.
  • Blood glucose
    • Apart from transient illness- or stress-induced hyperglycemia, a random whole-blood glucose concentration more than 200 mg/dL (11 mmol/L) is diagnostic for diabetes, as is a fasting whole-blood glucose concentration exceeding 120 mg/dL (7 mmol/L). In the absence of symptoms, the physician must confirm these results on a different day. Most children with diabetes detected due to symptoms have a blood glucose level of at least 250 mg/dL (14 mmol/L).

       

    • Blood glucose tests using capillary blood samples, reagent sticks, and blood glucose meters are the usual methods for monitoring day-to-day diabetes control.
  • Glycated hemoglobin
    • Glycosylated hemoglobin derivatives (HbA1a, HbA1b, HbA1c) are the result of a nonenzymatic reaction between glucose and hemoglobin. A strong correlation exists between average blood-glucose concentrations over an 8- to 10-week period and the proportion of glycated hemoglobin. The percentage of HbA1c is more commonly measured. Normal values vary according to the laboratory method used, but nondiabetic children generally have values in the low-normal range. At diagnosis, diabetic children unmistakably have results above the upper limit of the reference range.
    • Measurement of HbA1c levels is the best method for medium- to long-term diabetic control monitoring. The Diabetes Control and Complications Trial (DCCT) has demonstrated that patients with HbA1c levels around 7% had the best outcomes relative to long-term complications. Check HbA1c levels every 3 months. Most clinicians aim for HbA1c values of 7-9%. Values less than 7% are associated with an increased risk of severe hypoglycemia; values more than 9% carry an increased risk of long-term complications.
  • Renal function tests: If the child is otherwise healthy, renal function tests typically are not required.
  • Islet cell antibodies
    • Islet cell antibodies may be present at diagnosis but are not needed to diagnose IDDM.

       

    • Islet cell antibodies are nonspecific markers of autoimmune disease of the pancreas and have been found in as many as 5% of unaffected children. Other autoantibody markers against islet cells are known (eg, those against glutamate decarboxylase [GAD antibodies]), but these generally are unavailable.
  • Thyroid function tests
    • Because early hypothyroidism has few easily identifiable clinical signs in children, children with IDDM may have undiagnosed thyroid disease.

       

    • Untreated thyroid disease may interfere with diabetes management. Check thyroid function annually if thyroid antibodies are present.
  • Antithyroid antibodies: This test indicates risk of present or potential thyroid disease.
  • Antigliadin antibodies
    • Some children with IDDM may have or develop celiac disease. Positive antigliadin antibodies, especially specific antibodies (eg, antiendomysial) are important risk markers.

       

    • If antibody tests are positive, jejunal biopsy is required to confirm or refute a diagnosis of celiac disease.

Imaging Studies:

  • No routine imaging is required.

Other Tests:

  • Oral glucose tolerance test
    • While unnecessary to diagnose IDDM, an oral glucose tolerance test can exclude the diagnosis of diabetes when hyperglycemia or glycosuria are recognized in the absence of typical causes (eg, intercurrent illness, steroid therapy), or when the patient's condition includes renal glucosuria.
    • Obtain a fasting blood sugar level, then administer a PO glucose load (2 g/kg for children aged <3 y, 1.75 g/kg for children aged 3-10 y [max 50 g], or 75 g for children aged >10 y). Check blood glucose concentration again after 2 hours. A fasting whole-blood glucose level of more than 120 mg/dL (6.7 mmol/L) or a 2-hour value more than 200 mg/dL (11 mmol/L) indicate diabetes. Mild elevations, however, may not indicate diabetes when the patient has no symptoms and no diabetes-related antibodies.
  • Lipid profile
    • Lipid profiles usually are abnormal at diagnosis because of increased circulating triglycerides caused by gluconeogenesis.
    • Primary lipid disorders rarely result in diabetes.
    • Hyperlipidemia with poor metabolic control is common.
  • Urinary albumin: Beginning at age 12 years, perform annual urinalysis to test for a slightly increased albumin excretion rate (AER), referred to as microalbuminuria, which is an indicator of risk for diabetic nephropathy.

TREATMENT
Medical Care:

  • All children with IDDM require insulin therapy.
  • Only children with serious dehydration or metabolic derangement or with serious intercurrent illness require prolonged IV rehydration as inpatients.
  • A well-organized diabetes care team can provide all necessary instruction and support in an outpatient setting. The only immediate requirement is to train the child or family to check blood glucose, to administer insulin injections, and to recognize and treat hypoglycemia. The patient and/or family also should know how to contact the team.

Consultations:

  • Always involve an experienced dietitian in the patient's care, typically as a regular member of the diabetes care team.
  • Ophthalmology review may be needed at diagnosis if a cataract is suspected. All pubertal or older children with diabetes need a careful eye examination annually to identify and, if necessary, treat diabetes-related eye complications.
  • Access to psychological counseling is desirable, preferably from a member of the diabetes care team.

Diet: Dietary management is an essential component of diabetes care. Diabetes is an energy metabolism disorder, and before insulin was discovered, children with diabetes could be kept alive by a diet severely restricted in carbohydrate and energy intake. These measures led to a long tradition of strict carbohydrate control and unbalanced diets. More recent dietary management of diabetes emphasizes a healthy, balanced diet, high in carbohydrates and fiber and low in fat.

  • The following are universal recommendations:
    • Carbohydrates should provide 50-60% of daily energy intake. (No more than 10% of carbohydrates should be from sucrose or other refined carbohydrates.)

       

    • Fat should provide less than 30%.

       

    • Protein should provide 10-20%.

       

    • View these recommendations in the patient's cultural context.
  • The aim of dietary management is to balance the child's food intake with insulin dose and activity and to keep blood glucose concentrations as close as possible to reference ranges, avoiding extremes of hyperglycemia and hypoglycemia.
    • Adequate intake of complex carbohydrates (eg, cereals) is important before bedtime to avoid nocturnal hypoglycemia.
    • The dietitian should develop a diet plan for each child to suit individual needs and circumstances. Regularly review and adjust the plan to accommodate the patient's growth and life-style changes.

Activity:

  • IDDM requires no restrictions on activity; exercise has real benefits for a child with diabetes.
  • Most children can adjust their insulin dosage and diet to cope for all forms of exercise.
  • Children and their supervisors must be able to recognize and treat symptoms of hypoglycemia.

MEDICATION
Insulin always is required to treat IDDM. Attempts are being made to develop alternative routes to subcutaneous administration (eg, inhalation). Although insulin originally was derived from animal sources, recombinant human insulin now is used. Human insulins have shorter duration of action.

Insulin has 3 basic formulations: short-acting (eg, regular, soluble, lispro), medium- or intermediate-acting (eg, isophane, lente), and long-acting (eg, ultralente).

Regular insulin is bound to either protamine (eg, isophane) or zinc (eg, lente, ultralente) in order to prolong the duration of action. Combinations of isophane and regular or lispro insulin also are available in a variety of concentrations that vary around the world, ranging from 10/90 mixtures (ie, 10% regular, 90% isophane) to 50/50 mixtures.

A wide variety of insulin-injection devices exist, ranging from a simple syringe and needle, to semiautomatic pen injector devices. Increasing numbers of young people use insulin pumps to deliver continuous SC insulin with bolus doses at meal times.

Insulin is administered in 2-4 injections daily. The traditional method has been twice daily of a combination of short and intermediate insulin. Recently, the basal bolus regimen of regular insulin before main meals and an intermediate insulin before bedtime has become more popular, at least with physicians.

Lispro insulin, an analogue of human insulin, is a recently introduced variant. Lispro has rapid onset of action, and shorter duration than modified regular (crystalline) insulin. These characteristics make it ideally suited for meal times, but its short duration of action requires twice-daily injections of isophane or lente.

Other insulin analogues are becoming available; short-, intermediate-, and long-acting analogues are designed to give more predictable patterns of action and eventually may replace more traditional forms.

Tailor the insulin dose to the individual child’s needs. As a rule of thumb, prepubertal children require between 0.5 and 1 U/kg/d, with between 60-70% administered in the morning and 30-40% in the evening. Insulin resistance is a feature of puberty, and some adolescents may require up to 2 U/kg/d. About a third of the administered insulin is a short-acting formulation and the remainder is a medium- to long-acting formulation. Basal bolus regimens have a higher proportion of short-acting insulin.
 

Drug Category: Antidiabetic agents -- Treatment of insulin-dependent DM, also NIDDM unresponsive to treatment with diet and/or PO hypoglycemics.

Drug Name
 		 Lispro insulin (Humalog) -- Onset of action is 10-30 min, peak activity is 1-2 h, and duration of action is 2-4 h.
Adult Dose Adjust to needs
Pediatric Dose Adjust to needs
Contraindications Documented hypersensitivity; hypoglycemia
Interactions Medications that may decrease hypoglycemic effects of insulin include acetazolamide, AIDS antivirals, asparaginase, phenytoin, nicotine isoniazid, diltiazem, diuretics, corticosteroids, thiazide diuretics, thyroid estrogens, ethacrynic acid, calcitonin, oral contraceptives, diazoxide, dobutamine phenothiazines, cyclophosphamide, dextrothyroxine, lithium carbonate, epinephrine, morphine sulfate, and niacin; medications that may increase hypoglycemic effects of insulin include calcium, ACE inhibitors, alcohol, tetracyclines, beta blockers, lithium carbonate, anabolic steroids, pyridoxine, salicylates, MAOIs, mebendazole, sulfonamides, phenylbutazone, chloroquine, clofibrate, fenfluramine, guanethidine, octreotide, pentamidine, and sulfinpyrazone
Pregnancy B - Usually safe but benefits must outweigh the risks.
Precautions Monitor glucose carefully; dose adjustments may be necessary in renal and hepatic dysfunction
Drug Name
 		 Regular insulin (Humulin R, Novolin R) -- Onset of action is 0.25-1 h, peak activity is 1.5-4 h, and duration of action is 5-9 h.
Adult Dose Adjust to needs
Pediatric Dose Adjust to needs
Contraindications Documented hypersensitivity; hypoglycemia
Interactions Medications that may decrease hypoglycemic effects of insulin include acetazolamide, AIDS antivirals, asparaginase, phenytoin, nicotine isoniazid, diltiazem, diuretics, corticosteroids, thiazide diuretics, thyroid estrogens, ethacrynic acid, calcitonin, oral contraceptives, diazoxide, dobutamine phenothiazines, cyclophosphamide, dextrothyroxine, lithium carbonate, epinephrine, morphine sulfate, and niacin; medications that may increase hypoglycemic effects of insulin include calcium, ACE inhibitors, alcohol, tetracyclines, beta blockers, lithium carbonate, anabolic steroids, pyridoxine, salicylates, MAOIs, mebendazole, sulfonamides, phenylbutazone, chloroquine, clofibrate, fenfluramine, guanethidine, octreotide, pentamidine, and sulfinpyrazone
Pregnancy B - Usually safe but benefits must outweigh the risks.
Precautions Dose adjustments may be necessary in renal and hepatic dysfunction
Drug Name
 		 Insulin NPH (Humulin N, Novolin N) -- Onset of action is 3-4 h, peak effect is in 8-14 h, and usual duration of action is 16-24 h.
Adult Dose Adjust to needs
Pediatric Dose Adjust to needs
Contraindications Documented hypersensitivity; hypoglycemia
Interactions Medications that may decrease hypoglycemic effects of insulin include acetazolamide, AIDS antivirals, asparaginase, phenytoin, nicotine isoniazid, diltiazem, diuretics, corticosteroids, thiazide diuretics, thyroid estrogens, ethacrynic acid, calcitonin, oral contraceptives, diazoxide, dobutamine phenothiazines, cyclophosphamide, dextrothyroxine, lithium carbonate, epinephrine, morphine sulfate, and niacin; medications that may increase hypoglycemic effects of insulin include calcium, ACE inhibitors, alcohol, tetracyclines, beta blockers, lithium carbonate, anabolic steroids, pyridoxine, salicylates, MAOIs, mebendazole, sulfonamides, phenylbutazone, chloroquine, clofibrate, fenfluramine, guanethidine, octreotide, pentamidine, and sulfinpyrazone
Pregnancy B - Usually safe but benefits must outweigh the risks.
Precautions Dose adjustments may be necessary in renal and hepatic dysfunction
Drug Name
 		 Protamine zinc (Ultralente) -- Onset of action is 2-3 h, peak activity is 4-8 h, and duration of action is 8-16 h.
Adult Dose Adjust to needs
Pediatric Dose Adjust to needs
Contraindications Documented hypersensitivity; hypoglycemia
Interactions Medications that may decrease hypoglycemic effects of insulin include acetazolamide, AIDS antivirals, asparaginase, phenytoin, nicotine isoniazid, diltiazem, diuretics, corticosteroids, thiazide diuretics, thyroid estrogens, ethacrynic acid, calcitonin, oral contraceptives, diazoxide, dobutamine phenothiazines, cyclophosphamide, dextrothyroxine, lithium carbonate, epinephrine, morphine sulfate, and niacin; medications that may increase hypoglycemic effects of insulin include calcium, ACE inhibitors, alcohol, tetracyclines, beta blockers, lithium carbonate, anabolic steroids, pyridoxine, salicylates, MAOIs, mebendazole, sulfonamides, phenylbutazone, chloroquine, clofibrate, fenfluramine, guanethidine, octreotide, pentamidine, and sulfinpyrazone
Pregnancy B - Usually safe but benefits must outweigh the risks.
Precautions Dose adjustments may be necessary in renal and hepatic dysfunction

FOLLOW-UP
 Further Inpatient Care:

  • Where a diabetes care team is available, admission usually is required only for children with DKA.

Further Outpatient Care:

  • Regular outpatient review with a specialized diabetes team improves both short- and long-term outcomes. Most teams have a nurse specialist or educator, dietitian, and a pediatrician with training in diabetes care. Other members could include a psychologist, a social worker, and an exercise specialist. Involvement with the team is intense over the first few weeks after diagnosis while family members learn about diabetes management.
  • Conduct a structured examination and review at least once annually to examine the patient for possible complications. Examination and review should include the following:
    • Growth assessment

       

    • Injection site examination

       

    • Retinoscopy or other retinal screening such as photography

       

    • Examination of hands, feet, and peripheral pulses for signs of limited joint mobility, peripheral neuropathy, and vascular disease

       

    • Evaluation for signs of associated autoimmune disease

       

    • BP

       

    • Urine examination for microalbuminuria

In/Out Patient Meds:

  • Insulin
  • Blood glucose testing strips
  • Urine ketone testing tablets or strips

Deterrence/Prevention:

  • Actively discourage patients from smoking because it markedly increases the risk of developing cardiovascular complications.
  • Discuss issues of sexual health with older children. Provide young women with information on pregnancy planning to ensure the best possible outcomes for themselves and their offspring.

Complications:

  • Hypoglycemia

     

    • Hypoglycemia probably is the most disliked and feared complication of diabetes, from the point of view of the child and the family. Children hate the symptoms of a hypoglycemic episode and the loss of personal control it may cause.

       

    • Insulin inhibits glucogenesis and glycogenolysis, while stimulating glucose uptake. In nondiabetic individuals, insulin production by the pancreatic islet cells is suppressed when blood glucose levels fall below 83 mg/dL (4.6 mmol/L). If insulin is injected in a treated diabetic child who has not eaten adequate amounts of carbohydrates, blood glucose levels progressively fall.

       

    • The brain depends upon glucose as a fuel. As glucose levels drop below 65 mg/dL (3.2 mmol/L) counterregulatory hormones (eg, glucagon, cortisol, epinephrine) are released, and symptoms of hypoglycemia develop. These symptoms include sweatiness, shaking, confusion, behavioral changes, and, eventually, coma when blood glucose levels fall below 30-40 mg/dL. The glucose level at which symptoms develop varies greatly from individual to individual (and from time to time in the same individual), depending in part on the frequency of hypoglycemic episodes, rate of fall of glycemia, and overall control.

       

    • Treat mild hypoglycemia by giving rapidly absorbed PO carbohydrate or glucose; for a comatose patient, administer IV glucose (preferably a 10% glucose solution). An alternative treatment is IM injection of the hormone glucagon, which stimulates the release of liver glycogen and releases glucose into the circulation. All treatments for hypoglycemia provide recovery in approximately 10 minutes.

       

    • Occasionally, a child with hypoglycemic coma may not recover within 10 minutes, despite appropriate therapy. Under no circumstances should further treatment be given, especially IV glucose, until blood glucose level is checked and still found subnormal. Overtreatment of hypoglycemia can lead to cerebral edema and death. If coma persists, seek other causes.

       

    • Hypoglycemia is a particular concern in children younger than 4 years because the condition may lead to possible intellectual impairment later in life.
  • Hyperglycemia

     

    • In an otherwise healthy individual, blood glucose levels usually do not rise above 180 mg/dL (9 mmol/L). In a child with diabetes, blood sugar levels rise if insulin is insufficient for a given glucose load. The renal threshold for glucose reabsorption is exceeded when blood glucose levels exceed 180 mg/dL (10 mmol/L), causing glycosuria with the typical symptoms of polyuria and polydipsia.

       

    • All children with diabetes experience episodes of hyperglycemia.
  • Diabetic ketoacidosis

     

    • DKA is much less common than hypoglycemia, but it is potentially far more serious, creating a life-threatening medical emergency.

       

    • Ketosis usually does not occur when insulin is present. In its absence, however, severe hyperglycemia, dehydration, and ketone production contribute to the development of DKA.
  • Injection-site hypertrophy

     

    • If children persistently inject their insulin into the same area, subcutaneous tissues may develop, causing unsightly lumps and adversely affecting insulin absorption. Moving the injection sites resolves the condition.

       

    • Fat atrophy also can occur, possibly in association with insulin antibodies. This condition is much less common but more disfiguring.
  • Diabetic retinopathy

     

    • The most common cause of acquired blindness in many developed nations, diabetic retinopathy is rare in the prepubertal child or within 5 years of onset of diabetes.

       

    • Prevalence and severity of retinopathy increases with age and is greatest in patients whose diabetic control is poor. Prevalence rates seem to be declining, yet an estimated 80% of people with IDDM develop retinopathy.

       

    • Diabetic retinopathy's first symptoms are dilated retinal venules and the appearance of capillary microaneurysms, a condition known as background retinopathy. These changes may be reversible or their progression may be halted with improved diabetic control, although some patient's conditions may worsen initially.

       

    • Subsequent changes in background retinopathy are characterized by increased vessel permeability and plasma leaking that form hard exudates, followed by capillary occlusion and flame-shaped hemorrhages. The patient may not notice these changes unless the macula is involved. Laser therapy may be required at this stage to prevent further visual loss. Proliferative retinopathy follows with further vascular occlusion, retinal ischemia, proliferation of new retinal blood vessels and fibrous tissue, then progressing to hemorrhage, scarring, retinal detachment, and blindness. Prompt retinal laser therapy may prevent blindness in the later stages, so regular screening is vital.
  • Diabetic nephropathy and hypertension

     

    • Diabetic nephropathy's exact mechanism is unknown. Peak incidence is in postadolescents, 10-15 years after diagnosis, and may involve up to 30% of people with IDDM.

       

    • Microalbuminuria is the first evidence of nephropathy. This slightly increased AER has been defined as a ratio of first morning-void urinary albumin to creatinine exceeding 10 mg/mmol, or as a timed overnight AER of more than 20 mcg/min but less than 200 mcg/min. Early microalbuminuria may resolve. Glomerular hyperfiltration occurs, as do abnormalities of the glomerular basement membrane and glomeruli.

       

    • In a patient with nephropathy, AER increases until frank proteinuria develops, and this may progress to renal failure. Blood pressure rises with increased AER, and hypertension accelerates the progression to renal failure.

       

    • Progression may be delayed or halted by improved diabetes control, by administration of angiotensin-converting enzyme inhibitors (ACE inhibitors), and by aggressive blood pressure control.

       

    • Regular urine screening for microalbuminuria provides opportunities for early identification and treatment to prevent renal failure.
  • Diabetic neuropathy affects both the peripheral and autonomic nerves. Hyperglycemic effects on axons and microvascular changes in endoneural capillaries are neuropathy's 2 proposed mechanisms.

     

  • Autonomic changes involving cardiovascular control (eg, heart rate, postural responses) have been described in as many as 40% of children with diabetes. Cardiovascular control changes become more likely with increasing duration and worsening control.

     

  • In adults, peripheral neuropathy usually occurs as a distal sensory loss.
  • Macrovascular disease

     

    • While this complication is not seen in pediatric patients, it is a significant cause of morbidity and premature mortality in adults with diabetes.

       

    • People with IDDM have twice the risk of fatal myocardial infarction (MI) and stroke than people unaffected with diabetes; for women, the MI risk is 4 times greater. People with IDDM also have 4 times greater risk for atherosclerosis.

       

    • The combination of peripheral vascular disease and peripheral neuropathy can cause serious foot pathology.

       

    • Smoking, hypertension, hyperlipidemia, and poor diabetic control greatly increase the risk of vascular disease.
  • Associated autoimmune diseases are relatively common in children and include the following:

     

    • Hypothyroidism affects 2-5% of children with diabetes.

       

    • Hyperthyroidism affects 1% of children with diabetes; the condition usually is discovered at the time of diabetes diagnosis.

       

    • Although Addison disease is uncommon, affecting less than 1% of children with diabetes, it is a life-threatening condition that may reduce the insulin requirement and increase the frequency of hypoglycemia. (These effects also may be the result of unrecognized hypothyroidism.)

       

    • Celiac disease, associated with an abnormal sensitivity to gluten in wheat products, probably is a form of autoimmune disease.

       

    • Necrobiosis lipoidica probably is another form of autoimmune disease. This condition usually, but not exclusively, is found in patients with IDDM. Necrobiosis lipoidica affects 1-2% of children and may be more common in children with poor diabetic control.
  • Limited joint mobility, primarily affecting hands and feet, is believed associated with poor diabetic control.

     

    • Originally described in approximately 30% of patients with IDDM, limited joint mobility occurs in 50% of patients older than 10 years who have had diabetes longer than 5 years. The condition restricts joint extension, making it difficult to press the hands flat against each other. The skin of patients with severe joint involvement has a thickened and waxy appearance.

       

    • Limited joint mobility is associated with increased risks for diabetic retinopathy and nephropathy. Improved diabetes control over the past several years appears to have reduced the frequency of these additional complications by an approximate 4-fold factor. More recent patients also have markedly fewer severe joint mobility limitations.

Prognosis:

  • Apart from severe DKA or hypoglycemia, IDDM has little immediate morbidity.
  • The risk of complications relates to diabetic control. With good management, patients can expect to lead full, normal, and healthy lives.

Patient Education:

  • Education is a continuing process involving the child, family, and all members of the diabetes team. The following strategies may be employed:
  • Children should wear some form of medical identification such as a medic alert bracelet or necklace.

MISCELLANEOUS
Medical/Legal Pitfalls:

  • Diabetes is missed easily in an infant or preschool child. If in doubt, check the urine for glucose.
  • DKA may present as respiratory distress.
  • Overzealous or inadequate treatment of hypoglycemia can lead to serious consequences.
  • Addison disease rarely develops but is easily missed and potentially fatal.
  • Failure to examine regularly for complications, especially renal and ophthalmic, can be detrimental.

Special Concerns:

  • Pregnancies should be planned carefully and should be managed to achieve healthy outcomes for mother and infant. Preconceptual normalization of blood sugars and folic acid supplements reduce the otherwise increased risk of congenital heart disease and neural tube defects. Blood sugar control during pregnancy must be strict to avoid hypoglycemia, which may damage the fetus, or persistent hyperglycemia, which leads to fetal gigantism, premature delivery, and increased infant morbidity and mortality.
  • Awareness of hypoglycemia becomes impaired over time, and severe hypoglycemia can occur without warning. Hypoglycemia is more likely to affect people who maintain low blood sugar levels and who already suffer frequent hypoglycemia attacks.
 

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