eMedicine Specialties > Endocrinology > Diabetes Mellitus
Diabetes Mellitus, Type 1: Treatment & Medication
Updated: Jul 2, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
Treatment of this disease requires a multidisciplinary approach by physician, nurse, and dietitian.
- Type 1 diabetes mellitus (DM) patients require insulin therapy to control initial hyperglycemia and maintain serum electrolytes and hydration. At times, the first incidence of ketoacidosis is followed by a symptom-free period during which patients do not need treatment. This "honeymoon period" follows the initial treatment, in which the disease remits and the patient requires little or no insulin. This remission is due to a partial return of endogenous insulin, which may last for several weeks or months (and sometimes 1-2 y). Ultimately, however, the disease recurs, and patients require insulin therapy.
- Initiation of insulin therapy in adults: The initial daily dose is calculated depending upon the weight of the patient. This dose is usually divided so that one half is administered before breakfast, one fourth before dinner, and one fourth at bedtime. After selecting the initial dose, adjust the amounts, types, and timing depending on plasma glucose levels. Adjust the dose to maintain preprandial plasma glucose at 80-150 mg/dL (ie, 4.44-8.33 mmol/L). The insulin dose is often adjusted in increments of 10% at a time, and the effects are assessed over about 3 days before making any further changes. More frequent adjustments of regular insulin can be made if risk of hypoglycemia is present.
- Initiation of insulin therapy in children
- Children with moderate hyperglycemia but without ketonuria or acidosis may be started with a single daily subcutaneous injection of 0.3-0.5 U/kg of intermediate-acting insulin alone.
- Children with hyperglycemia and ketonuria but without acidosis or dehydration may be started on 0.5-0.7 U/kg of intermediate-acting insulin and subcutaneous injections of 0.1 U/kg of regular insulin at 4- to 6-hour intervals.
- Insulin schedules
- Multiple subcutaneous insulin injections are administered to control hyperglycemia after meals and to maintain normal plasma glucose levels throughout the day. This may increase the risks of hypoglycemia. Therefore, patients should be well educated about their disease and about self-monitoring of plasma glucose levels.
- About 25% of the total daily dose is administered as intermediate-acting insulin at bedtime, with additional doses of rapid-acting insulin before each meal (4-dose regimen). These patients may need additional intermediate- or long-acting insulin in the morning for all-day coverage. Patients should adjust their daily dosage(s) based on their self-monitoring of glucoses before each meal and at bedtime. Patients should also assess their plasma glucose levels at 2-4 o'clock in the morning at least once per week during the first few weeks of treatment and thereafter as indicated.
- Continuous subcutaneous insulin infusion: This intensive insulin treatment uses a small battery-operated infusion pump that administers a continuous subcutaneous infusion of rapid-acting insulin. This provides selected, programmed basal rate(s) of insulin and a manually administered bolus dose before each meal. The patient self-monitors preprandial glucose levels to adjust the bolus dose(s). This method provides better control than with multiple injections. Hypoglycemia is common initially with pump therapy, but, once metabolic control is achieved, the risk is the same as with multiple injections.
Surgical Care
Pancreatic transplantation is a possibility in some referral centers and is performed most commonly with simultaneous kidney transplantation for end-stage renal disease.
Consultations
These patients should be referred to an endocrinologist for multidisciplinary management.
- These patients should have a complete retinal examination by an ophthalmologist at least once a year.
- The patients with significant proteinuria or a reduced creatinine clearance should be referred to a nephrologist.
Diet
One of the first steps in managing type 1 DM is diet control. According to the ADA policy, the diet treatment is based upon nutritional assessment and treatment goals. Diet recommendations should be made in view of the patient's eating habits and lifestyle.
- Diet management includes education about the timing, size, frequency, or composition of meals to avoid hypoglycemia or postprandial hyperglycemia. All patients on insulin should receive a comprehensive diet plan that includes a daily caloric intake prescription; recommendations for amounts of dietary carbohydrate, fat, and protein; and how to divide calories between meals and snacks. A professional dietitian should be involved to create the individual diet plan.
- In these patients, the caloric distribution is important; a recommended distribution consists of 20% of daily calories for breakfast, 35% for lunch, 30% for dinner, and 15% for late evening snack.
- The minimum protein requirement for good nutrition is 0.9 g/kg/d (range = 1-1.5 g/kg/d), but a reduced protein intake is indicated in cases of nephropathy.
- Fat intake should be limited to 30% or less of the total calories, and a low-cholesterol diet is recommended.
- Patients should consume sucrose in moderation and increase their fiber intake. In some cases, midmorning and midafternoon snacks are important to avoid hypoglycemia.
Activity
Exercise is an important aspect of diabetes management. Patients should be encouraged to exercise regularly. Educate the patients about the effects of exercise on the blood glucose level. If patients are planning to participate in rigorous exercise for more than 30 minutes, they may develop hypoglycemia. To prevent hypoglycemia, they either can decrease the insulin by 10-20% or can have an extra snack. These patients must maintain their hydration status during exercise.
Medication
Insulin injected subcutaneously is the first-line therapy in the treatment of type 1 diabetes. The different types of insulin are based upon their times of onset and durations of action. Short-, intermediate-, and long-acting insulins are available. Regular, lispro, and aspart insulins are the only types that can be administered intravenously.
- Human insulin currently is the only species of insulin available in the United States, and it is less antigenic than previously used animal-derived varieties.
- Rapid-acting insulins include regular insulin, lispro, and aspart insulin. Regular insulin is a preparation of zinc insulin crystals in solution. Its onset of action is 0.5-1 h, it peaks at 2.5-5 h, and duration of action is 6-8 h. Lispro insulin is a form of regular insulin that is genetically engineered with the reversal of the amino acids lysine and proline in the B chain. Aspart insulin has aspartic acid substituted for proline in position 28 of the B chain. Both of these insulins are absorbed more quickly and have a rapid onset (5-10 min), peak (1 h), and duration (4 h) of action. Therefore, they have the advantage that they may be administered shortly before eating. Semilente insulin is like regular insulin and is a slightly slower rapid-acting insulin. It contains zinc insulin microcrystals in an acetate buffer and is not readily available in the United States.
- Intermediate-acting insulins include neutral protamine Hagedorn (NPH) insulin, which contains a mixture of regular and protamine zinc insulin, and lente insulin, which contains 30% semilente insulin and 70% ultralente insulin in an acetate buffer.
- Long-acting insulins include ultralente insulin, containing large zinc insulin crystals in an acetate buffer, and insulin glargine, a newer long-acting insulin that has no peak and produces a relatively stable level lasting more than 24 hours. Both insulins can supply basal 24-hour insulin with a single daily injection.
- Mixtures of insulin preparations with different onsets and durations of action frequently are administered in a single injection by drawing measured doses of 2 preparations into the same syringe immediately before use. The exception is insulin glargine, which should not be mixed with any other form of insulin. Preparations that contain a mixture of 70% NPH and 30% regular human insulin (ie, Novolin 70/30, Humulin 70/30) are available, as is Humulin 50/50, but the fixed ratios of intermediate-acting to rapid-acting insulin may restrict their use. In addition, a 25/75 mixture of NPH and lispro insulin is available.
Rapid-, short-, and intermediate-acting insulins
Rapid- and short-acting insulins have the most rapid onsets of action and are used whenever quick glucose utilization is needed (eg, before meals, when blood glucose >250 mg/dL). They stimulate proper utilization of glucose by the cells and reduce blood sugar levels.
Intermediate-acting insulins have slower onsets of action and longer durations of action and are usually administered in combination with faster-acting insulins to maximize benefits of a single injection.
Regular, aspart, lispro, NPH, and lente insulins (NovoLog, Apidra, Humulin R, Novolin N, Novolin R)
Insulin is routinely provided in preparations containing 100 U/mL (U-100 insulin). However, concentrations up to U-500 are available for persons with marked insulin resistance. A multiple-dose insulin injection device, commonly referred to as an insulin pen, uses a cartridge containing several days' dosage. Insulin should be refrigerated but never frozen. Most insulin preparations, however, are stable at room temperature for months, which facilitates their use at work and when traveling.
Glulisine is a human insulin analog produced by rDNA technology using a nonpathogenic laboratory strain of Escherichia coli (K12). It differs from human insulin by replacement of asparagine at B3 position with lysine; 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 that of regular human insulin when administered IV. After SC administration, insulin glulisine has faster onset and shorter duration of action compared with regular human insulin. It is useful to regulate mealtime blood glucose elevation.
Aspart insulin (NovoLog) onset of action is 0.25 h, peak effect is in 1-3 h, and usual duration of action is 3-5 h. Glulisine insulin (Apidra) onset of action is 0.25 h, peak effect is in 1-1.5 h, and usual duration of action is 1-2.5 h.
Regular insulin (Humulin R, Novolin R) onset of action is 0.5-1 h, peak effect is in 2-3 h, and usual duration of action is 8-12 h.
Isophane insulin suspension (Novolin N) onset of action is 1-1.5 h, peak effect is in 4-12 h, and usual duration of action is 24 h.
Insulin zinc suspension (Lente) onset of action is 1-2.5 h, peak effect is in 8-12 h, and duration of action is 18-24 h.
Adult
0.5-1 U/kg/d SC in divided doses; titrate dose to maintain a premeal and bedtime glucose level of 80-140 mg/dL
Pediatric
Administer as in adults
Medications that may decrease hypoglycemic effects of insulin include acetazolamide, AIDS antivirals, asparaginase, phenytoin, nicotine, isoniazid, diltiazem, diuretics, corticosteroids, thiazide diuretics, thyroxine, estrogens, ethacrynic acid, calcitonin, oral contraceptives, diazoxide, dobutamine, phenothiazines, cyclophosphamide, 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
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; monitor glucose carefully; dose adjustments of insulin may be necessary in patients diagnosed with renal and hepatic dysfunction
Insulin, inhaled (Exubera)
10/18/07 – Discontinued by manufacturer. Pfizer Inc announced that it is no longer making inhaled insulin (Exubera). The decision is not based on any safety concerns but is due to economic feasibility resulting from too few patients taking the inhaled insulin. Pfizer will work with physicians to transition patients from inhaled insulin to other treatment options over the next several months. Exubera was approved by the US Food and Drug Administration in January 2006 as the first inhaled insulin.
It stimulates proper use of glucose by cells and reduces blood glucose levels. It is an inhaled powder form of recombinant human insulin (rDNA). Inhaled insulin is indicated for adults with type 1 or type 2 diabetes mellitus. It acts rapidly (onset similar to rapid-acting insulins [ie, 10-12 min]) and reaches peak level more quickly than regular insulin. Peak insulin level averages 49 min (range, 30-90 min) for inhaled and 105 min (range, 60-240 min) for regular SC insulin. Duration is similar to regular SC insulin (ie, 6 h). Available as 1- and 3-mg blister packs inserted into inhaler. A fraction of the total particle mass is emitted as fine particles capable of reaching the deep part of the lungs. Actual amount of insulin delivered to the lungs depends on individual patient factors (eg, inspiratory flow). In vitro test conditions measured emitted and fine particle doses for blister packs: 1-mg blister delivers an emitted dose of 0.53 mg and a fine particle dose of 0.4 mg fine; 3-mg blister delivers an emitted dose of 2.03 mg and a fine particle dose of 1 mg.
Adult
Approximate guidelines for initial doses (based on patient weight and consumption of 3 meals/d; administer within 10 min ac
30-39.9 kg: 1 mg/meal
40-59.9 kg: 2 mg/meal
60-79.9 kg: 3 mg/meal
80-99.9 kg: 4 mg/meal
100-119.9 kg: 5 mg/meal
120-139.9 kg: 6 mg/meal
Note: Prescribing information details approximate equivalent to regular SC human insulin; inhaled insulin 1 mg blister is approximately equivalent to 8 IU of regular SC human insulin
Pediatric
Not established
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, 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
Bronchodilators or other inhaled drugs may alter absorption of inhaled insulin; consistent timing of dose, relative to inhaled insulin, is recommended
Documented hypersensitivity; hypoglycemia; smoking or having discontinued smoking within 6 mo before initiating inhaled insulin; poorly controlled lung disease
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
Most commonly reported adverse effect is hypoglycemia; hyperthyroidism may increase renal clearance of insulin (more insulin may be needed to treat hyperkalemia); hypothyroidism may delay insulin turnover (less insulin may be needed to treat hyperkalemia); monitor glucose level carefully; dose adjustments may be necessary in patients with renal and/or hepatic dysfunction; may cause insulin antibody formation; may cause cough, shortness of breath, sore throat, and dry mouth; effectiveness not established in patients with asthma, bronchitis, or emphysema; may decrease pulmonary function (ie, FEV1, DLCO) (baseline tests for lung function recommended before initiating treatment and q6-12mo); dispensed with medication guide for patients
Long-acting insulins
These insulins offer a very long duration of action and, when combined with faster-acting insulins, offer better glucose control for some patients.
On July 1, 2009, the US Food and Drug Administration (FDA) issued an early communication to health care practitioners regarding 4 recently-published observational studies that describe the possible association of insulin glargine (Lantus) with an increased risk of cancer.2 Insulin glargine is a long-acting human insulin analogue approved for once-daily dosing.
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 that considered to be 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 risk that actually exists, 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.
Extended insulin zinc suspension (Ultralente)
Onset of action is 4-8 h, peak effect is in 16-18 h, and usual duration of action is >32 h.
Adult
10 U SC qd; adjust according to patient response
Pediatric
<6 years: Not established
>6 years: Administer as in adults
Medications that may decrease hypoglycemic effects of insulin include acetazolamide, AIDS antivirals, asparaginase, phenytoin, nicotine, isoniazid, diltiazem, diuretics, corticosteroids, thiazide diuretics, thyroxine, estrogens, ethacrynic acid, calcitonin, oral contraceptives, diazoxide, dobutamine, phenothiazines, cyclophosphamide, 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
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
Use only if solution is clear and colorless; administer SC only; do not mix glargine 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
Insulin detemir (Levemir)
Indicated for qd or bid SC administration for individuals with type 1 or 2 diabetes mellitus who require long-acting basal insulin for hyperglycemia control. Duration of action ranges from 5.7 h (low dose) to 23.2 h (high dose). Prolonged action is a result of slow systemic absorption of detemir molecules from injection site. Primary activity is regulation of glucose metabolism. Binds to insulin receptors and lowers blood glucose by facilitating cellular uptake of glucose into skeletal muscle and fat; also inhibits glucose output from liver. Inhibits lipolysis in adipocytes, inhibits proteolysis, and enhances protein synthesis.
Adult
Administer individualized dose SC qd or bid
Once-daily dosage: Administer with evening meal or hs
Twice-daily dosage: Administer second dose with evening meal, hs, or 12 h after morning dose
Persons currently receiving only basal insulin can switch to insulin detemir on unit-to-unit basis
For insulin-naive patients with type 2 diabetes inadequately controlled with oral antidiabetic drugs, initiate at 0.1-0.2 U/kg qd in evening, then adjust to achieve glycemic control
Pediatric
Not established
Numerous drugs may affect glucose metabolism, requiring dose adjustment
Drugs that may reduce blood glucose–lowering effect of insulin are corticosteroids, danazol, diuretics, sympathomimetic agents (eg, epinephrine, albuterol, terbutaline), isoniazid, phenothiazine derivatives, somatropin, thyroid hormones, estrogens, and progestogens (eg, oral contraceptives)
Drugs that may increase blood glucose–lowering effect of insulin and susceptibility to hypoglycemia are oral antidiabetic drugs, ACE inhibitors, disopyramide, fibrates, fluoxetine, MAOIs, propoxyphene, salicylates, somatostatin analog (eg, octreotide), and sulfonamide antibiotics
Beta-blockers, clonidine, lithium salts, and alcohol may either potentiate or weaken blood glucose–lowering effect of insulin; pentamidine may cause hypoglycemia, which may sometimes be followed by hyperglycemia; sympatholytics (eg, beta-blockers, clonidine, guanethidine, reserpine) may reduce signs of hypoglycemia
Documented hypersensitivity
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 in thigh, abdominal wall, or upper arm; rotate injection site within same region; most common adverse effect is hypoglycemia (glucose monitoring required); do not dilute or mix with any other insulin; caution with renal or hepatic impairment (dose adjustment may be needed); injection site allergy or lipodystrophy may occur
Insulin Glargine (Lantus)
Stimulates proper utilization of glucose by the cells and reduce blood sugar levels. Onset of action is 4-8 h, peak effect is in 16-18 h, and usual duration of action is 24 h.
Adult
10 U SC qd; adjust according to patient response; safety of insulin glargine in pregnancy has not been established
Pediatric
<6 years: Not established
>6 years: Administer as in adults
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, 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, 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 US Food and Drug Administration (FDA) has issued an early communication regarding the association, based on 4 observational studies, between insulin glargine and an increased cancer risk; the FDA states that because of inconsistencies across the studies, further evaluation is required before this association can be confirmed
Amylin analogs
Elicit endogenous amylin effects by delaying gastric emptying, decreasing postprandial glucagon release, and modulating appetite.
Pramlintide acetate (Symlin)
Synthetic analogue of human amylin, a naturally occurring hormone made in pancreatic beta cells. Slows gastric emptying, suppresses postprandial glucagon secretion, and regulates food intake owing to centrally mediated appetite modulation. Indicated to treat type 1 or type 2 DM in combination with insulin. Administered before mealtime for patients who have not achieved desired glucose control despite optimal insulin therapy. Helps achieve lower blood glucose levels after meals, less fluctuation of blood glucose levels during the day, and improvement of long-term control of glucose levels (ie, Hb A1C levels) compared with insulin alone. Additionally, less insulin use and a reduction in body weight observed.
Adult
15 mcg SC ac initially; titrate upward in 15-mcg increments (if no significant nausea occurs for 3-7 d) to maintenance dose of 30-60 mcg/dose; insulin dose must initially be decreased during initiation phase; once target pramlintide dose achieved, optimize insulin to maintain glycemic control
Pediatric
Not established
Do not use with other drugs that slow gastric emptying (eg, anticholinergic agents such as atropine) or drugs that slow intestinal nutrient absorption (eg, alpha-glucosidase); may delay absorption of concomitantly administered oral drugs; to avoid this effect, administer other drug 1 h before or 2 h after pramlintide
Documented hypersensitivity to pramlintide, any of its components, or metacresol; gastroparesis; hypoglycemia unawareness
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
Increases risk of insulin-induced severe hypoglycemia, especially with type 1 DM or gastroparesis; reduce insulin dose in all patients (either type 2 or type 1 DM) when initiating therapy (monitor blood glucose and adjust insulin dose during initiation phase); common adverse effects include GI complaints, especially nausea (risk decreased when dose increased gradually); always use separate insulin syringe to measure and administer, do not mix in same syringe as insulin (insulin alters pharmacokinetics); may cause local redness, swelling, or itching at injection site; do not administer unless ingesting major meal (ie, >250 calories or 30 g of carbohydrates)
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 |
| References |
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Further Reading
Keywords
type 1 DM, type 1 diabetes, type 2 diabetes mellitus, type II diabetes mellitus, autoimmune diabetes mellitus, juvenile-onset diabetes, ketosis-prone diabetes, insulin-dependent diabetes mellitus, IDDM, brittle diabetes mellitus, diabetic ketoacidosis, DKA, maturity-onset diabetes of the young, MODY
