eMedicine Specialties > Pediatrics: General Medicine > Endocrinology
Diabetes Mellitus, Type 1: Treatment & Medication
Updated: Jul 2, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Treatment
Medical Care
- All children with type 1 diabetes mellitus (T1DM) require insulin therapy.
- Only children with significant dehydration, persistent vomiting, or metabolic derangement, or with serious intercurrent illness, require inpatient management and intravenous rehydration.
- 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 levels, to administer insulin injections, and to recognize and treat hypoglycemia. The patient and/or family should have 24-hour access to advice and know how to contact the team.17
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 children with diabetes aged 12 years and older need a careful annual eye examination, either by direct ophthalmoscopy or high-quality retinal photography to identify and, if necessary, treat diabetes-related eye complications.
- Access to psychological counseling and support is desirable, preferably from a member of the diabetes care team. Consensus guidelines produced by The International Society of Pediatric and Adolescent Diabetes (ISPAD) made it clear that diabetes management and metabolic control were very strongly influenced by psychological factors.18 Their most recent practice guidelines recommend the availability of professionals with appropriate psychological expertise within the diabetes clinical management 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 the most recent consensus recommendations:19
- Carbohydrates should provide 50-55% of daily energy intake. (No more than 10% of carbohydrates should be from sucrose or other refined carbohydrates.)
- Fat should provide 30-35% of daily energy intake.
- Protein should provide 10-15% of daily energy intake.
- 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.
- The ability to estimate the carbohydrate content of food (carbohydrate counting) is particularly useful for those children who give fast-acting insulin at meal times either by injection or insulin pump, as it allows for a more precise matching of food and insulin.
- Adequate intake of complex carbohydrates (eg, cereals) is important before bedtime to avoid nocturnal hypoglycemia, especially for children having twice-daily injections of mixed insulin.
- 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 lifestyle changes.
- Low-carbohydrate diets as a management option for diabetes control have regained popularity in recent years. Logic dictates that the lower the carbohydrate intake, the less insulin is required. No trials of low-carbohydrate diets in children with type 1 diabetes mellitus have been reported, and such diets cannot be recommended at the present.
Activity
- Type 1 diabetes mellitus 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 with all forms of exercise.
- The current guidelines are increasingly sophisticated and allow children to compete at the highest levels in sport.20
- Children and their caretakers must be able to recognize and treat symptoms of hypoglycemia.
- Hypoglycemia following exercise is most likely after prolonged exercise involving the legs, such as walking, running or cycling. It may occur many hours after exercise has finished and even affect insulin requirements the following day.
- A large presleep snack is advisable following intensive exercise.
Medication
Insulin is always required to treat insulin-dependent diabetes mellitus (IDDM). Attempts are being made to develop alternative routes to subcutaneous administration. In January 2006, a human insulin (rDNA origin) inhalant powder (Exubera) was approved by the US Food and Drug Administration (FDA) for use in adults. Although insulin was originally derived from animal sources, recombinant human insulin and the newer "designer" insulin analogues are now most commonly used. On October 18, 2007, Pfizer Inc announced that it is no longer making inhaled insulin (Exubera). The decision was not based on any safety concerns but was due to economic feasibility resulting from too few patients taking the inhaled insulin.
Insulin has 3 basic formulations: short-acting (eg, regular, soluble, lispro, aspart, glulisine), medium-acting or intermediate-acting (eg, isophane, lente, detemir), and long-acting (eg, ultralente, glargine).
Regular or soluble 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, lispro or aspart insulins are also 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.
The recent development of insulin analogues have attempted to address some of the shortcomings of traditional insulin.21 Insulins lispro and aspart have a more rapid onset of action and shorter duration, making them more suitable for bolusing at mealtimes and for short-term correction of hyperglycemia. An intermediate-acting insulin, detemir, has a similar profile of action to isophane but is more pharmacologically predictable, while glargine has a relatively flat profile of action, lasting some 18-26 hours and seems especially suitable as a once-daily basal injection. Despite their apparent advantages over traditional insulins, no evidence suggests a long-term advantage of the analogue insulins in terms of metabolic control or complication rates.22
- The observational studies evaluated large patient databases, and all reported some association between insulin glargine and other insulin products with various types of cancer. The duration of the observational studies was shorter than what is considered necessary to evaluate for drug-related cancers. Additionally, findings were inconsistent within and across the studies, and patient characteristics differed across treatment groups. These issues raise further questions about the actual risk and, therefore, warrants further evaluation.
- The FDA states that patients should not stop taking their insulin without consulting their physician. An ongoing review by the FDA will continue to update the medical community and consumers with additional information as it emerges. Statements from the American Diabetes Association and the European Association for the Study of Diabetes called the findings conflicting and inconclusive and cautioned against overreaction.
With so many various insulins and mixtures available, a wide range of possible injection regimens exist. These can be broadly categorized into 4 types, as follows:
- Twice-daily combinations of short-acting and intermediate-acting insulin.
- Multiple injection regimens, using once-daily or twice-daily injections of long-acting or intermediate-acting insulin and short-acting insulins given at each meal
- A combination of the above 2 regimens, with a morning injection of mixed insulin, an afternoon premeal injection of short-acting insulin and an evening injection of intermediate-acting or long-acting insulin
- Continuous subcutaneous insulin infusion (CSII) using an insulin pump
Although controlled clinical trials suggest improved short-term metabolic control in children using multiple injections or CSII,24 international comparisons do not support any particular insulin regimen,25,26 and all have their advantages and disadvantages.
A wide variety of insulin-injection devices are available, including a simple syringe and needle, semiautomatic pen injector devices, and needle-free jet injectors. Increasing numbers of young people use insulin pumps to deliver continuous subcutaneous insulin, with bolus doses at meal times.
Tailor the insulin dose to the individual child's needs. For instance, if using a twice-daily regimen, then, 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 as much as 2 U/kg/d. About one third of the administered insulin is a short-acting formulation and the remainder is a medium-acting to long-acting formulation. Basal bolus regimens have a higher proportion of short-acting insulin. Typically, 50% of the total daily dose is given as long-acting or intermediate-acting insulin. CSII uses only short-acting insulins, most often the analogues lispro or aspart.
Antidiabetic agents
These agents are used for treatment of insulin-dependent diabetes mellitus and also for non–insulin-dependent diabetes mellitus (NIDDM) unresponsive to treatment with diet and/or oral hypoglycemics.
Insulin lispro (Humalog)
Onset of action is 10-30 min, peak activity is 1-2 h, and duration of action is 2-4 h.
Adult
0.5-1 U/kg/d SC initially; adjust doses to achieve premeal and bedtime blood glucose levels of 80-140 mg/dL (4-7.5 mmol/L)
Pediatric
0.5-1 U/kg/d SC initially
Adjust doses to achieve premeal and bedtime blood glucose levels of:
<5 years: 100-200 mg/dL (5.5-10 mMol/L)
>5 years: 80-140 mg/dL (4-7.5 mMol/L)
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, PO 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
Documented hypersensitivity; hypoglycemia
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Due to prompt onset of action, administer within 15 min before or immediately after a meal; monitor glucose carefully; dose adjustments may be necessary in renal and hepatic dysfunction
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
Adjust to needs
Pediatric
Adjust to needs
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, PO 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
Documented hypersensitivity; hypoglycemia
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Dose adjustments may be necessary in renal and hepatic dysfunction
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
Adjust to needs
Pediatric
Adjust to needs
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, PO 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
Documented hypersensitivity; hypoglycemia
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Dose adjustments may be necessary in renal and hepatic dysfunction
Insulin aspart (NovoLog)
Onset of action is 10-30 min, peak activity is 1-2 h, and duration of action is 3-6 h. Homologous with regular human insulin, with the exception of single substitution of amino acid proline by aspartic acid in position B28. Produced by recombinant DNA technology. Insulin lowers blood glucose levels by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production. Inhibits lipolysis in the adipocyte. Inhibits proteolysis. Enhances protein synthesis. Insulin is the principal hormone required for proper glucose use in normal metabolic processes.
Adult
0.5-1 U/kg/d SC initially; adjust doses to achieve premeal and bedtime blood glucose levels of 80-140 mg/dL (4-7.5 mMol/L)
Pediatric
0.5-1 U/kg/d SC initially
Adjust doses to achieve premeal and bedtime blood glucose levels of:
<5 years: 100-200 mg/dL (5.5-10 mMol/L)
>5 years: 80-140 mg/dL (4-7.5 mMol/L)
Medications that may decrease hypoglycemic effects of insulin include acetazolamide, AIDS antivirals, asparaginase, phenytoin, nicotine, isoniazid, diltiazem, diuretics, corticosteroids, thiazide diuretics, thyroid hormone, estrogens, ethacrynic acid, calcitonin, PO 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, MAO inhibitors, mebendazole, sulfonamides, phenylbutazone, chloroquine, clofibrate, fenfluramine, guanethidine, octreotide, pentamidine, and sulfinpyrazone
Documented hypersensitivity; hypoglycemia
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Hyperthyroidism may increase renal clearance of insulin and may need more insulin to treat hyperkalemia; hypothyroidism may delay insulin turnover, requiring less insulin to treat hyperkalemia; due to prompt onset of action, administer within 15 min before or immediately after a meal; monitor glucose carefully; dose adjustments may be necessary in renal and hepatic dysfunction
Insulin glargine (Lantus)
Long-acting insulin analogue. Typical onset of action from 1-2 h, duration 20-26 h
Adult
Usually 50% of total daily dose of insulin (0.25-0.5 U/kg); adjust to needs
Pediatric
Licensed age varies between nations (2-6 y); adjust dose as indicated but similar to adult
Medications that may decrease hypoglycemic effects of insulin include acetazolamide, AIDS antivirals, asparaginase, phenytoin, nicotine, isoniazid, diltiazem, diuretics, corticosteroids, thiazide diuretics, thyroid hormone, estrogens, ethacrynic acid, calcitonin, PO 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, MAO inhibitors, mebendazole, sulfonamides, phenylbutazone, chloroquine, clofibrate, fenfluramine, guanethidine, octreotide, pentamidine, and sulfinpyrazone
Documented hypersensitivity; hypoglycemia
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Administer at the same time each day; use only if solution is clear and colorless; administer SC only; do not mix with any other insulin or solution; hyperthyroidism may increase renal clearance of insulin and may need more insulin to treat hyperkalemia; hypothyroidism may delay insulin turnover, requiring less insulin; monitor glucose carefully; dose adjustments of insulin may be necessary in patients diagnosed with renal and hepatic dysfunction
July 1, 2009 - The FDA has issued an early communication regarding the association of insulin glargine and an increased cancer risk based on 4 observational studies; because of inconsistencies across the studies, further evaluation is required before this association can be confirmed
Insulin glulisine (Apidra)
Human insulin analog produced by rDNA technology using a nonpathogenic laboratory strain of Escherichia coli (K12). Differs from human insulin by replacement of asparagine at B3 position with lysine, and the lysine at the B29 position is replaced by glutamic acid.
Insulin regulates glucose metabolism by stimulating peripheral glucose uptake by skeletal muscle and fat, and inhibits hepatic glucose production.
Glucose lowering is equipotent to regular human insulin when administered IV. After SC administration, insulin glulisine has more rapid onset and shorter duration of action compared to regular human insulin. Useful to regulate mealtime blood glucose elevation.
Adult
Individualize dose; intended for intermittent SC injection with meals or use by external infusion pump
Pediatric
0.5-1 U/kg/d SC initially;
Adjust doses to achieve premeal and bedtime blood glucose levels of:
<5 years: 100-200 mg/dL (5.5-10 mMol/L)
>5 years: 80-140 mg/dL (4-7.5 mMol/L)
Corticosteroids, danazol, diazoxide, diuretics, sympathomimetic agents (eg, epinephrine, albuterol, terbutaline), glucagon, isoniazid, phenothiazines, growth hormone, thyroid hormone, estrogen, progestogens, protease inhibitors, and atypical antipsychotics (eg, olanzapine, clozapine) may increase blood glucose and reduce glucose lowering effect of insulin; PO antidiabetic agents, ACE inhibitors, disopyramide, fibrates, fluoxetine, MAOIs, pentoxifylline, propoxyphene, salicylates, and sulfonamides may decrease blood glucose and cause additive effects to insulin
Documented hypersensitivity; hypoglycemia
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Hyperthyroidism may increase renal clearance of insulin and may need more insulin to treat hyperkalemia; hypothyroidism may delay insulin turnover, requiring less insulin to treat hyperkalemia; due to prompt onset of action, administer within 15 min before or immediately after a meal; monitor glucose carefully; dose adjustments may be necessary in renal and hepatic dysfunction
More on Diabetes Mellitus, Type 1 |
| Overview: Diabetes Mellitus, Type 1 |
| Differential Diagnoses & Workup: Diabetes Mellitus, Type 1 |
 Treatment & Medication: Diabetes Mellitus, Type 1 |
| Follow-up: Diabetes Mellitus, Type 1 |
| Multimedia: Diabetes Mellitus, Type 1 |
| References |
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Further Reading
Keywords
diabetes mellitus type 1, insulin-dependent diabetes, IDM, insulin-dependent diabetes mellitus, IDDM, growth-onset diabetes, type I diabetes, type 1 diabetes, DM, diabetes, type 1 DM, T1DM, childhood diabetes, childhood diabetes mellitus, childhood-onset diabetes, childhood-onset diabetes mellitus, diabetes in childhood, diabetes mellitus in childhood, juvenile-onset diabetes, juvenile-onset diabetes mellitus, ketosis-prone diabetes, autoimmune diabetes mellitus, brittle diabetes mellitus, diabetic ketoacidosis, DKA, maturity-onset diabetes of the young, MODY, chamber-pot dropsy, thirst disease, sugar disease, sugar sickness
