Diabetes Health Center

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Re: Diabetes Health Center

مشاركةبواسطة دكتور كمال سيد » الجمعة يناير 18, 2019 10:49 pm

Approach Considerations
Patients with type 1 diabetes mellitus (DM) require lifelong insulin therapy. Most require 2 or more injections of insulin daily, with doses adjusted on the basis of self-monitoring of blood glucose levels. Long-term management requires a multidisciplinary approach that includes physicians, nurses, dietitians, and selected specialists.

In some patients, the onset of type 1 DM is marked by an episode of diabetic ketoacidosis (DKA) but is followed by a symptom-free “honeymoon period” in which the symptoms remit and the patient requires little or no insulin. This remission is caused by a partial return of endogenous insulin secretion, and it may last for several weeks or months (sometimes for as long as 1-2 years). Ultimately, however, the disease recurs, and patients require insulin therapy.

Often, the patient with new-onset type 1 DM who presents with mild manifestations and who is judged to be compliant can begin insulin therapy as an outpatient. However, this approach requires close follow-up and the ability to provide immediate and thorough education about the use of insulin; the signs, symptoms, and treatment of hypoglycemia; and the need to self-monitor blood glucose levels.

The American Diabetes Association (ADA) recommends using patient age as one consideration in the establishment of glycemic goals, with targets for preprandial, bedtime/overnight, and hemoglobin A1c (HbA1c) levels. [5] In 2014, the ADA released a position statement on the diagnosis and management of type 1 diabetes in all age groups. The statement includes a new pediatric glycemic control target of HbA1c of less than 7.5% across all pediatric age groups, replacing earlier guidelines that specified different glycemic control targets by age. The adult HbA1c target of less than 7% did not change. Individualized lower or higher targets may be used based on patient need. [72, 73]

In addition to diagnosis and management, the new statement also covers screening for long-term complications, workplace management, diabetes in older patients, and diabetes in pregnancy, and recommends unimpeded access to glucose test strips for blood glucose testing and use of continuous glucose monitoring. [72, 73]

Although patients with type 1 DM have normal incretin response to meals, administration of exogenous glucagonlike peptide 1 (GLP-1) reduces peak postprandial glucose by 45%. Long-term effects of exogenously administered GLP-1 analogues warrant further studies. [74]

Pancreatic transplantation for patients with type 1 DM isg a possibility in some referral centers. It is performed most commonly with simultaneous kidney transplantation for end-stage renal disease (ESRD).

The American Diabetes Association's Standards of Medical Care in Diabetes for type 1 and 2 diabetes highlight
(recommendations most relevant to primary care. [75] (See Guidelines

The care of patients with type 1 diabetes mellitus is summarized below.

Tight glycemic control
The association between chronic hyperglycemia and increased risk of microvascular complications in patients with type 1 DM was demonstrated in the Diabetes Control and Complications Trial (DCCT). [76] In that trial, intensive therapy designed to maintain normal blood glucose levels greatly reduced the development and progression of retinopathy, microalbuminuria, proteinuria, and neuropathy, as assessed over 7 years.

The DCCT ended in 1993. However, the Epidemiology of Diabetes Interventions and Complications Study (EDIC), an observational study that continues to follow the patients previously enrolled in the DCCT, has demonstrated continued benefit from intensive treatment. [77, 78]

Benefits

Benefits of tight glycemic control include not only continued reductions in the rates of microvascular complications but also significant differences in cardiovascular events and overall mortality. These benefits occurred even though subjects in the intensively treated group and those in the standard treatment group maintained similar HbA1c levels (about 8%), starting 1 year after the DCCT ended. It is postulated that a “metabolic memory” exists and that better early glycemic control sets the stage for outcomes many years in the future.

Increasing HbA1c levels correlated with increasing risk of developing heart failure in a study of 20,985 patients with type 1 DM. Thus, improved glycemic control should prevent heart failure as well. [79]

Risks

For many patients, the HbA1c target should be less than 7%, with a premeal blood glucose level of 80–130 mg/dL. However, targets should be individualized.

Individuals with recurrent episodes of severe hypoglycemia, cardiovascular disease, advanced complications, substance abuse, or untreated mental illness may require higher targets, such as an HbA1c of less than 8% and preprandial glucose levels of 100-150 mg/dL. The 2011 American Association of Clinical Endocrinologists (AACE) guidelines support the creation of individualized targets that consider these factors as part of a comprehensive treatment plan. [80]

Although tight glycemic control is beneficial, an increased risk of severe hypoglycemia accompanies lower blood glucose levels. The 2011 AACE guidelines for developing a comprehensive care plan emphasize that hypoglycemia should be avoided. [66]

In patients with type 1 DM, recurrent and chronic hypoglycemia has been linked to cognitive dysfunction. [81] This has important implications in the management of children with type 1 DM. [82]

An 18-year follow-up of the DCCT by Jacobson et al found that HbA1c levels and retinal and renal complications were independently linked to cognitive declines. No relation with macrovascular risk factors or severe hypoglycemic events was found. A smoking history was modestly associated with decrements in learning, memory, spatial information processing, and psychomotor efficiency. This information is useful in advising patients with type 1 DM interested in preserving cognitive function

https://emedicine.medscape.com/article/117739-treatment

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Re: Diabetes Health Center

مشاركةبواسطة دكتور كمال سيد » الجمعة يناير 18, 2019 10:51 pm

Insulin Therapy
Types of insulin
Rapid-, short-, intermediate-, and long-acting insulin preparations are available. Various pork, beef, and beef-pork insulins were previously used; however, in the United States, recombinant human insulin is now used almost exclusively. Commercially prepared mixtures of insulin are also available.

Rapid-acting insulins include lispro, glulisine, and aspart insulin. Lispro insulin is a form of regular insulin that is genetically engineered with the reversal of the amino acids lysine and proline at B28,29 in the B chain. Glulisine insulin substitutes glutamic acid for lysine in position B29. Aspart insulin substitutes aspartic acid for proline in position 28 of the B chain.

These insulins are absorbed more quickly and have a rapid onset of action (5-10 minutes), a short interval to peak action (45-75 minutes), and a short duration of action (2-4 hours). Therefore, they can be administered shortly before eating. In addition, neutral protamine Hagedorn (NPH) insulin will not inhibit the action of insulin lispro when the 2 agents are mixed together right before injection; this is not true of regular insulin.

A rapid-acting inhaled insulin powder (Afrezza) for types 1 and 2 diabetes mellitus was approved by the FDA in June 2014. It is regular insulin but is considered rapid-acting because it peaks at 12-15 minutes and returns to baseline levels at about 160 minutes. Approval was based on a study involving over 3,000 patients over a 24-week period. In persons with type 1 diabetes, the inhaled insulin was found to be noninferior to standard injectable insulin when used in conjunction with basal insulin at reducing hemoglobin A1c. In persons with type 2 diabetes, the inhaled insulin was compared to placebo inhalation in combination with oral diabetic agents and showed a statistically significant lower hemoglobin A1c. [100, 101]

Short-acting insulin includes regular insulin. Regular insulin is a preparation of zinc insulin crystals in solution. When it is administered subcutaneously, its onset of action occurs in 0.5 hours, its peak activity comes at 2.5-5 hours, and its duration of action is 4-12 hours.

The standard strength of regular insulin is 100 U/mL (U-100), but 500 U/mL (U-500) insulin is increasingly used, albeit mostly in type 2 DM. Accidental prescribing of U-500 rather than U-100 is a potential safety issue. [102] A study by de la Pena et al found that although the overall insulin exposure and effects of 500 U/mL insulin are similar to those of 100 U/mL insulin, peak concentration was significantly lower with U-500, and the effect after the peak was prolonged; areas under the curve were similar for the 2 strengths. [103]

Both regular human insulin and rapid-acting insulin analogues are effective at lowering postprandial hyperglycemia in various basal bolus insulin regimens used in type 1 DM. Rapid-acting insulin analogues may be slightly better at lowering HbA1c and are preferred by most US diabetologists, but the differences are clinically insignificant. [104]

In September 2017, the FDA approved the rapid-acting insulin aspart Fiasp for the treatment of adults with diabetes. This human insulin analog is formulated with niacinamide, which aids in speeding the initial absorption of insulin. Dosing can occur at the beginning of a meal or within 20 minutes after the meal commences. In a study of adult patients with type 1 DM, Fiasp could be detected in the circulation about 2.5 minutes after it was administered. Maximum insulin levels occurred approximately 63 minutes after the drug’s administration. [105, 106]

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Re: Diabetes Health Center

مشاركةبواسطة دكتور كمال سيد » الجمعة يناير 18, 2019 10:53 pm

Semilente insulin is like regular insulin and is a rapid-acting insulin with a slightly slower onset of action. It contains zinc insulin microcrystals in an acetate buffer. It is not readily available in the United States.

Intermediate-acting insulins include NPH insulin, a crystalline suspension of human insulin with protamine and zinc. NPH provides a slower onset of action and longer duration of action than regular insulin does. The onset of action usually occurs at 1-2 hours, the peak effect is noted at 4-12 hours, and the duration of action is normally 14–24 hours.

Lente insulin is a suspension of insulin in buffered water that is modified by the addition of zinc chloride. This insulin zinc suspension is equivalent to a mixture of 30% prompt insulin zinc (Semilente) and 70% extended insulin zinc (Ultralente). It is not used in the United States.

Long-acting insulins used in the United States include insulin glargine (Lantus, Toujeo) and insulin detemir (Levemir). Insulin glargine has no peak and produces a relatively stable level lasting more than 24 hours. In some cases, it can produce a stable basal serum insulin concentration with a single daily injection, though patients requiring lower doses typically are given twice-daily injections. Insulin detemir has a duration of action that may be substantially shorter than that of insulin glargine but longer than those of intermediate-acting insulins.

Toujeo 300 U/mL is a newer dosage strength and form of insulin glargine than Lantus 100 U/mL, having been approved by the FDA in February 2016. Compared with those of Lantus 100 U/mL, the pharmacokinetic and pharmacodynamic profiles of Toujeo are more stable and prolonged; the duration of action exceeds 24 hours. Clinical trials showed comparable glycemic control between Lantus and Toujeo, although the trials noted the need for higher daily basal insulin doses (ie, 12-17.5%) with Toujeo. The risk for nocturnal hypoglycemia was lower with Toujeo in insulin-experienced patients with type 2 diabetes, but this was not the case for insulin-naïve patients with type 1 DM or for patients with type 2 DM. [107]

With its March 2018 approval by the FDA, Toujeo Max SoloStar became the highest capacity long-acting insulin pen on the market. Toujeo Max necessitates fewer refills and, for some diabetes patients, fewer injections to deliver the required Toujeo dosage. [108]

A new ultralong-acting basal insulin, insulin degludec (Tresiba), which has a duration of action beyond 42 hours, has also been approved by the FDA. It is indicated for diabetes mellitus types 1 and 2. A combination product of insulin degludec and the rapid-acting insulin aspart was also approved (Ryzodeg 70/30). Approval was based on results from the BEGIN trial [109, 110, 111] that showed noninferiority to comparator productions. The cardiovascular outcomes trial (DEVOTE) comparing cardiovascular safety of insulin degludec to that of insulin glargine in patients with type 2 DM is ongoing.

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 exceptions are insulin glargine and insulin detemir, which should not be mixed with any other form of insulin. Preparations that contain a mixture of 70% NPH and 30% regular human insulin (eg, Novolin 70/30, Humulin 70/30, Ryzodeg 70/30) are available, but the fixed ratios of intermediate-acting or long-acting to rapid-acting insulin may restrict their use.

An ultrafast-acting insulin aspart formulation for mealtimes (Fiasp), for adult patients with type 1 or 2 DM, was approved in January 2017 for use in Canada and the Europe Union. The drug contains conventional mealtime insulin aspart in combination with two ingredients—vitamin B3 and the amino acid L-arginine—that are meant to allow faster insulin absorption so the medication can better mimic natural physiologic insulin. Unlike in the European Union, however, the new formulation is not approved for insulin pumps in Canada. The product has not yet been approved for use in the United States. [112]

Insulin glargine and cancer

Controversy has arisen over a disputed link between insulin glargine and cancer. On July 1, 2009, the FDA issued an early communication regarding a possible increased risk of cancer in patients using insulin glargine (Lantus). [113] The FDA communication was based on 4 observational studies that evaluated large patient databases and found some association between insulin glargine (and other insulin products) and various types of cancer.

The validity of the link remains in question, however. The duration of these observational studies was shorter than that considered necessary to evaluate for drug-related cancers. Additionally, findings were inconsistent within and across the studies, and patient characteristics differed across treatment groups.

In a study by Suissa et al, insulin glargine use was not associated with an increased risk of breast cancer during the first 5 years of use. The risk tended to increase after 5 years, however, and significantly so for the women who had taken other forms of insulin before starting insulin glargine. [114]

A study by Johnson et al found the same incidences for all cancers in patients receiving insulin glargine as in those not receiving insulin glargine. Overall, no increase in breast cancer rates was associated with insulin glargine use, although patients who used only insulin glargine had a higher rate of cancer than those who used another type of insulin. This finding was attributed to allocation bias and differences in baseline characteristics. [115]

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Re: Diabetes Health Center

مشاركةبواسطة دكتور كمال سيد » الجمعة يناير 18, 2019 10:55 pm

Common insulin regimens
The goal of treatment in type 1 DM is to provide insulin in as physiologic a manner as possible. Insulin replacement is accomplished by giving a basal insulin and a preprandial (premeal) insulin. The basal insulin is either long-acting (glargine or detemir) or intermediate-acting (NPH). The preprandial insulin is either rapid-acting (lispro, aspart, or glulisine) or short-acting (regular). Currently, NPH insulin is being used less frequently, whereas insulin glargine and insulin detemir are being used more frequently.

For patients on intensive insulin regimens (multiple daily injections or insulin pumps), the preprandial dose is based on the carbohydrate content of the meal (the carbohydrate ratio) plus a correction dose if their blood glucose level is elevated (eg, an additional 2 U of rapid-acting insulin to correct the blood glucose from a level of 200 mg/dL to a target of 100 mg/dL). This method allows patients more flexibility in caloric intake and activity, but it requires more blood glucose monitoring and closer attention to the control of their diabetes.

Common insulin regimens include the following:

Split or mixed – NPH with rapid-acting (eg, lispro, aspart, or glulisine) or regular insulin before breakfast and supper

Split or mixed variant – NPH with rapid-acting or regular insulin before breakfast, rapid-acting or regular insulin before supper, and NPH before bedtime (the idea is to reduce fasting hypoglycemia by giving the NPH later in the evening)

Multiple daily injections (MDI) – A long-acting insulin (eg, glargine or detemir) once a day in the morning or evening (or twice a day in about 20% of patients) and a rapid-acting insulin before meals or snacks (with the dose adjusted according to the carbohydrate intake and the blood glucose level)

Continuous subcutaneous insulin infusion (CSII) – Rapid-acting insulin infused continuously 24 hours a day through an insulin pump at 1 or more basal rates, with additional boluses given before each meal and correction doses administered if blood glucose levels exceed target levels

Insulin is sensitive to heat and exposure to oxygen. Once a bottle of insulin is open, it should be used for no more than 28 days and then discarded; even if there is still some insulin in the bottle, it may have lost its clinical effectiveness. Insulin kept in a pump reservoir for longer than 3 days may lose its clinical effectiveness (though insulin aspart has now been approved for use for as long as 6 days in a pump).

Sometimes, insulin distributed from the pharmacy has been exposed to heat or other environmental factors and therefore may be less active. If a patient is experiencing unexplained high blood sugar levels, new insulin vials should be opened and used.

Initiation of insulin therapy
The initial daily insulin dose is calculated on the basis of the patient’s weight. 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 according to the 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 any further changes are made. More frequent adjustments of regular insulin can be made if a risk of hypoglycemia is present.

Carbohydrate counting may be used to determine the meal-time insulin dose. Because patients may experience hyperglycemic episodes despite strict adherence to carbohydrate counting, particularly after meals that are high in protein or fat, Australian researchers developed an algorithm for estimating the mealtime insulin dose on the basis of measurements of physiologic insulin demand evoked by foods in healthy adults. The researchers showed that use of this algorithm improved glycemic control. [116]

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Re: Diabetes Health Center

مشاركةبواسطة دكتور كمال سيد » الجمعة يناير 18, 2019 10:56 pm

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.

Multiple daily injections

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). Where available, a basal insulin such as glargine or detemir is preferred to NPH. These patients may need additional intermediate- or long-acting insulin in the morning for all-day coverage.

Patients should adjust their daily dosage(s) on the basis of their self-monitoring of glucose levels before each meal and at bedtime. Patients should also assess their plasma glucose levels at 2:00-4:00 AM at least once per week during the first few weeks of treatment and thereafter as indicated.

Continuous subcutaneous insulin infusion

A small battery-operated infusion pump that administers a continuous subcutaneous infusion of rapid-acting insulin can provide 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).

The CSII method provides better control than the MDI method does. Initially, hypoglycemia is common with pump therapy, but once metabolic control is achieved, the risk is the same as with MDI. Bergenstal et al determined that sensor-augmented pump therapy led to better glycemic control and that more patients reached targets with this technology than with injection therapy. [117]

An Australian observational case-control study involving 690 children with type 1 diabetes found that CSII, in comparison with insulin injection therapy, yielded a long-term improvement in glycemic control, as well as a reduction in complications such as severe hypoglycemia and hospitalization for diabetic ketoacidosis (DKA). [118, 119] HbA1c improvement remained significant in the pump therapy cohort throughout 7 years of follow-up.

The rate of severe hypoglycemic events per 100 patient-years dropped from 14.7 to 7.2 with pump therapy but jumped from 6.8 to 10.2 events per 100 patient-years with injection therapy. [118, 119] Hospitalization rates for DKA were lower in children receiving pump therapy (2.3 per 100 patient-years) compared with those receiving injection therapy (4.7 per 100 patient-years) over 1160 patient-years of follow-up.

Increased bedtime doses of hypoglycemic agents with nighttime peaks in action may correct early morning hyperglycemia but may be associated with undesirable nocturnal hypoglycemia. Targeted CSII programming can facilitate the prevention of early-morning hyperglycemia in selected patients.

Changes in altitude may affect delivery from insulin pumps. During the flight of a commercial airliner (200 mm Hg pressure decrease), excess insulin delivery of 0.623% of cartridge volume was demonstrated as a result of bubble formation and expansion of preexisting bubbles. [120]

The American Association of Clinical Endocrinologists and American College of Endocrinology released a consensus statement on insulin pump management: [121]

Based on currently available data, continuous subcutaneous insulin infusion (CSII) is justified for basal-bolus insulin therapy in patients with type 1 diabetes mellitus.

Only providers whose practice can assume full responsibility for a comprehensive pump management program should offer this technology.

The ideal CSII candidate is a patient with type 1 diabetes mellitus or intensively management insulin-dependent type 2 diabetes mellitus who is currently performing 4 or more insulin injections and 4 or more self-monitored blood glucose measurements daily; is motivated to achieve optima blood glucose control; is willing and able to carry out the tasks that are required to use this complex and time-consuming therapy safely and effectively; and is willing to maintain frequent contact with their health care team.

Adult patients

At CSII initiation, the patient should have daily contact with the pump trainer. a return visit with the endocrinologist/diabetologist/advanced practice nurse is advised within 3-7 days after CSII initiation.

Educational consults should be scheduled weekly or biweekly at first, then periodically as needed.

Specialist follow-up visits should be scheduled at least monthly until the pump regimen is stabilized, then at least once every 3 mo.

Pediatric patients

CSII is indicated for pediatric patients with elevated hemoglobin A1C (HbA1C) levels on injection therapy; frequent, severe hypoglycemia; widely fluctuating glucose levels; a treatment regimen that compromises lifestyle; and microvascular complications and/or risk factors for macrovascular complications.

Ideal pediatric candidates are those with motivated families who are committed to monitoring blood glucose 4 or more times per day and have a working understanding of basic diabetes management.

Patient age and duration of diabetes should not be factors in determining the transition from injections to CSII.

Local allergic reactions
Generalized insulin allergy is rare. Symptoms occur immediately after the injection and include urticaria, angioedema, pruritus, bronchospasm, and, rarely, circulatory shock. As a rule, allergy may be treated with antihistamines. Some cases may require epinephrine and intravenous (IV) steroids.

Local allergic reactions can occur at the site of insulin injections and can cause pain, burning, local erythema, pruritus, and induration. These complications are less common with the human insulins now in use than with the animal insulins once widely employed. Such reactions usually resolve spontaneously without any intervention.

Local fat atrophy or hypertrophy at injection sites was common with animal insulins but is rare with human insulin and insulin analogues. Patients do not require any specific treatment of local fat hypertrophy, but injection sites should be rotated. Changing to a different insulin preparation may be necessary. [122]

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Re: Diabetes Health Center

مشاركةبواسطة دكتور كمال سيد » الجمعة يناير 18, 2019 10:58 pm

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Re: Diabetes Health Center

مشاركةبواسطة دكتور كمال سيد » الجمعة يناير 18, 2019 11:00 pm

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Re: Diabetes Health Center

مشاركةبواسطة دكتور كمال سيد » الجمعة يناير 18, 2019 11:07 pm

Glycemic Control During Serious Medical Illness and Surgery

https://emedicine.medscape.com/article/ ... atment#d14


Glycemic Control During Pregnancy

https://emedicine.medscape.com/article/ ... atment#d15

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Re: Diabetes Health Center

مشاركةبواسطة دكتور كمال سيد » الجمعة يناير 18, 2019 11:10 pm

Type 1 Diabetes Mellitus Questions & Answers

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