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Are You Familiar With Insulin Resistance?

July 24, 2011 By Leave a Comment

The body produces insulin but doesn’t use it correctly- is the simplest explanation for insulin resistance. However, there are more specific details to the body’s response in people that are insulin resistant.

Our bodies’ breakdown food into a substance called glucose. Glucose is also known as blood sugar. After eating the blood glucose rises. Our body’s response to this rise is the pancreas increases insulin levels to allow cells in our body to take the glucose and use it for energy. This is what occurs when the body is healthy and not diabetic.

When a person is identified as insulin resistance, insulin is not used correctly in their body to make energy in the muscle, fat and liver cells. The body responds by requesting or needing more insulin to make these cells work correctly. The pancreas that makes insulin incorrectly produces more insulin as a result of the muscle, fat and liver cells response that they don’t have enough insulin. However, the additional insulin not only goes to these cells but to all cells in the body. The body will respond to these abnormal levels by beginning to develop diabetes. 

If your body is insulin resistant chances of you becoming diabetic and having heart disease increases dramatically. There are other complications that can occur with development of diabetes such as blindness, deafness, amputations and kidney failure.

Several factors can contribute to patients that become insulin resistant. Obesity, lack of physical activity and a genetic factor have been identified as aspects contributing to this condition. Many of these patients also have other medical conditions such as high blood pressure, high cholesterol, and excess weight around the middle of their body.

Insulin resistant and pre-diabetic people usually don’t have any symptoms that can be identified by their physician or that they report to their physician. Insulin resistant disorder/syndrome can only be detected by measuring the insulin in the blood. Most physicians’ offices don’t carry out the test that can determine if a patient is insulin resistant because of the cost. The test is called euglycemic clamp and it is very costly and complex. Your physician may send you to a health care facility such as a hospital to have the test performed.  Some physicians will verify if a patient is pre-diabetic. The pre-diabetic test is a more reasonably priced test that can be performed in the office. The information your physician receives back from the test(s) performed will determine further medical care. If the test reveals the patient has a higher than normal blood sugar level, he may request the more expensive test performed.  However, the medical recommendations and treatment for insulin resistance and pre-diabetes are very similar.

You can reverse insulin resistance with physical activity and weight loss. By doing both of these insulin resistant patients can avoid becoming a type 2 diabetic or delaying it for quite a while. Physical activity is especially important because it makes your muscle cells use blood sugar for energy. Therefore, all of the excessive insulin in your body is being used with physical activity and exercise. In addition, a diabetic diet can also be of great benefit. Foods that cause your blood sugar to rise rapidly should be avoided and other foods that don’t should be increased.

With the diabetic diet foods that should be increased are those that include flour. For example, bread, spaghetti, macaroni, bagels, rolls, crackers, cookies and pretzels. Also it’s a good idea to eat processed corn products and white rice. Eat fruits and root vegetables only with other foods.

Through modification of your diet and physical activity the hope is you can avoid medication to control your insulin irregularities in your body. Some patients are able to modify these two things enough to address other diseases such as high blood pressure and high cholesterol. A good diet and physical exercise is great for treatment of all sorts of diseases and disorders in addition to a great preventative measure for avoiding diseases. It helps your body maintain good health or become healthier to fight or sometimes even cure diseases.

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Insulin Therapy 101 – Insulin Injection Basics

July 24, 2011 By Leave a Comment

Insulin is a hormone produced by your pancreas whose primary function is to lower blood sugar. It does this by binding to insulin receptors on the cell wall which open glucose transporters. Once the glucose transporters are opened by the action of insulin, glucose can flow freely from the blood into the cell.

If you are insulin dependent your body relies on insulin injections in order to function correctly. This is either because your pancreas is not secreting any insulin, as in type 1 diabetes), or else the insulin that your pancreas is making is not doing its job properly, as in type 2 diabetes.

Before we jump into discussing the various insulin regimens, I need to first explain two terms which you will come across frequently:

Basal insulin – This is the injection of a long-acting insulin which mimics the insulin secretion of the pancreas. A single basal shot of insulin continues to act slowly throughout the day, therefore you only need to inject it once or twice daily. These long-acting insulins are “peakless” which means that they try and maintain the same glucose level throughout the day, unlike the fast acting insulins which result in a rapid decrease in blood sugar.

Bolus insulin – A bolus is a medical term for a single dose. Bolus insulin is given when you eat food in order to counteract the rapid increase in blood glucose after a meal. Bolus insulins are typically fast-acting, some of which start bringing down blood glucose in a matter of minutes. They do not remain in your system for long, being metabolized and excreted out of the body usually within a few hours.

So, to summarise… basal insulin keeps your blood sugar stable in the absence of food, but when you eat you need to take a bolus of fast acting insulin in order to counteract the sudden increase in blood sugar which comes from the breakdown of carbohydrate into glucose.

Insulin is always necessary for the treatment of type 1 diabetes, because there is a complete lack of the hormone in these patients. Type 2 diabetics do not usually require insulin until the disease has progressed to a point where the patient has become highly resistant to insulin, or when oral antidiabetic medications are no longer enough to keep blood glucose levels down.

A patient with insulin dependent type 2 diabetes has to use insulin in the same way as type 1 diabetics. However, there is a difference in that type 2 diabetics usually have to take much larger doses of insulin than type 1 patients because they have become so resistant to the effects of insulin.

For many type 2 diabetics, the addition of a long acting (basal) insulin such as Lantus or Levemir is usually enough to provide enough help to assist the body’s own insulin in doing its job. If this is still not effective enough, a basal dose can be taken in addition to fast acting boluses of insulin at mealtimes.

These come premixed under certain brand names, a popular one is a 70/30 mix (70% long acting, 30% fast acting) called humulin or mixtard. These are usually taken before breakfast and supper.

However, the combination of basal and bolus injections provides much tighter glucose control and is a more flexible system than taking premixed insulin. This is because you can vary the amount and timing of the bolus to match what type of food you eat and when you eat it.

With mixtures of insulin such as the 70/30 mix, you have to take it on a rigid schedule, and you can only eat a certain number of carbohydrates each day and at a scheduled time. You are not able to vary the timing of the injections because they contain both slow acting and fast acting insulin, and you are not able to eat more or less food depending on how hungry you are that day.

Depending on the insulin regime prescribed by your doctor, you may have to inject insulin via a traditional syringe. However, the majority of patients now are using injection pens which come pre-filled with insulin as they are much easier to use. In either case, the following basics apply:

Step 1: If using a syringe, roll the insulin vial (or the syringe itself if it has been pre-filled) between the palms of your hands a number of times before filling the syringe to redistribute any particles that may have settled to the bottom. This ensures an even concentration of insulin in each dose. The same applies to insulin pens, but they should also be shaken as most pens have a small glass ball inside which can move around and mix the insulin thoroughly.

Step 2: Choose an injection site and pinch the skin slightly. Position the syringe or pen so that the insulin is injected under the fatty layer of the skin. Note that a 45 degree angle is best for children and adults who are very thin, otherwise a 90 degree angle may be more appropriate.

Step 3: You should rotate your injection site regularly. Insulin is best absorbed through the abdominal area so rotating injection sites in this area is ideal. You could visualize your abdomen as a grid of 8 squares. Assign to each square a particular day and change to a new one each day of the week.

1. Subsequent injections should be delivered at least 1 inch away from the previous injection site.

2. It is not necessary to disinfect the injection site with an alcohol swab as long as your skin is clean.

3. If necessary, insulin may be injected through clothing, but this is not recommended.

4. Never shake a vial of insulin as this creates air bubbles which can clog the syringe.

5. Never mix one type of insulin with another in a single syringe. This can make it’s effects erratic.

6. Try not to inject insulin into muscle tissue. It is painful and the insulin is absorbed too quickly and cause hypoglycemia.

Insulin pumps are normally used in type 1 diabetes however they can work as effectively for insulin dependent type 2 diabetics also.

Some advantages of using an insulin pump include:

You change your infusion site once every 3 days, so if you have a dislike of needles, insulin pumping is better than having to inject yourself times a day.

You will use less insulin with a pump than on injections. Insulin pumps only use fast acting insulin which is more efficient than the slow acting types. Typically you use 20% less insulin when using a pump.

Because you have more control of the amount of insulin you take, if you are motivated, you can achieve much lower HbA1c (glucose average) than with injections. This improved control is due to the fact you can take doses that are not whole units, but fractions of a unit.

A new development in the area of insulin pumps is the advent of the artificial pancreas. This device combines an insulin pump with a continuous blood glucose meter, and automatically calculates how much insulin you need, minute by minute. This device is not currently on the market, but foundations such as the JDRF have invested a lot of money into it’s R&D. Human trials are currently underway.

Not everyone is suited to pump therapy, and it usually reserved for cases of type 1 diabetes or insulin dependent type 2 diabetes. In order to be successful at using an insulin pump:

You need to be good at counting carbohydrates. You have to manually program the pump with the number of carbohydrates you are going to eat. It then calculates the dose of insulin to give you. You need to be comfortable working with technology. If you are unable to basic devices such as a cell phone, then the insulin pump is not for you. However, as you are reading this information on your computer, this is likely not the case. You need to be patient in order to give the pump a chance to impress you. It usually takes at least a week or two before your glucose levels reach a healthy level. It will also be at least several more weeks after that before you become confidant with adjusting the device. You need to have a cool head rather than anxiety prone. When your glucose level starts to seem a little scary you have to quickly figure out what changes you need to make. Your doctor will be able to assist you with the learning curve at first, but you will eventually have to cope with the device on your own as the lag time between seeing a problem and getting help is too long for another person to control your pump for you. Finally, you must be willing to test your blood glucose level with a glucometer about 8 times per day and more often when you are making adjustments to your routine.

Dr. Michael Murphy is an endocrinologist from Ireland. He has extensive knowledge on the topic of diabetes and has had many years of experience working with diabetic patients.

Visit BloodSugarSimplified.com for expert information written by a practicing endocrinologist. Up-to-date and easy to understand articles to answer all your questions about diabetes.

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Insulin therapy in type 1 diabetes mellitus

July 24, 2011 By Leave a Comment

Article by Richard Graydon, M.D, PhD

INTRODUCTION — The Diabetes Control and Complications Trial (DCCT) and other smaller studies demonstrated that improved glycemic control with intensive insulin therapy in patients with type 1 diabetes mellitus led to graded reductions in retinopathy, nephropathy, and neuropathy. The Epidemiology of Diabetes Interventions and Complications (EDIC) follow-up study from the DCCT demonstrated that intensive insulin therapy also reduces cardiovascular morbidity and mortality. What was considered “intensive therapy” in the DCCT is now considered to be standard therapy for management of type 1 diabetes.

Optimal insulin therapy requires an understanding of insulin pharmacokinetics. A number of factors influence the pharmacokinetics of insulin, including: the insulin preparation, size of subcutaneous depot, injection technique, site of injection, and alterations in subcutaneous blood flow. These topics are reviewed in detail elsewhere.

Issues relevant to insulin therapy in patients with type 1 diabetes will be reviewed here. A review of its use in type 2 diabetes is found elsewhere. A general discussion of management of type 1 diabetes in children and adolescents is reviewed separately. Intensive insulin therapy for critically ill patients (who are not necessarily diabetic) is also reviewed elsewhere. Interactive cases focusing on insulin therapy are found elsewhere. A discussion of other medication (pramlintide) to be considered in the treatment of type 1 diabetes is presented elsewhere.PRETREATMENT CONSIDERATIONS — The term “conventional insulin therapy” is used to describe simpler non-physiologic insulin regimens, such as single daily injections, or two injections per day (usually a combination of regular or short-acting and NPH insulins, mixed together in the same syringe and given in fixed amounts before breakfast and dinner). The term “intensive insulin therapy” describes treatment with three or more injections per day or with continuous subcutaneous insulin infusion with an insulin pump.Intensive therapy aims to provide a more physiologic profile of insulin by administration of a basal level of insulin (delivered by daily or twice daily injections of a long-acting insulin preparation, or continuous subcutaneous delivery of a rapid insulin preparation via a pump) and premeal boluses of a short or rapid-acting insulin. The dose of the pre-meal bolus is determined by the ambient blood glucose level before the meal, the size and composition of the meal, and anticipated activity levels.

Intensive insulin therapy is recommended for the majority of patients with type 1 diabetes. However, it is important to emphasize that this regimen will be successful only if the patient is fully committed to it, has good understanding of the regimen, and is supported by a health care team with sufficient enthusiasm and expertise to educate the patient and to continuously monitor his or her progress.

Drawbacks to intensive insulin — Although intensive insulin therapy has clear benefits in patients with type 1 diabetes and probably has benefits in those with type 2 diabetes, it is important to consider the major drawbacks associated with this regimen:

A greater effort is required by the patient to manage and coordinate diet, activity, insulin administration, and blood glucose monitoring. The incidence of hypoglycemia may be increased up to threefold in patients with type 1 diabetes.Weight gain is more likely, which can limit patient compliance, particularly in women.

The cost of intensive insulin therapy (00 to 00/year) was about three times that of conventional treatment, based upon an analysis of the DCCT and costs from the early 1990s.

In spite of these drawbacks, intensive insulin therapy is recommended for the majority of patients with type 1 diabetes to prevent, slow, or even reverse the development of complications.

When to start intensive therapy — Studies suggest that intensive therapy should be started as early as possible following the diagnosis of type 1 diabetes. In 303 patients from the DCCT with early type 1 diabetes and residual beta-cell function who were randomly assigned to intensive or conventional insulin therapy, those receiving intensive therapy were slower to lose residual beta-cell function than the conventional therapy group (risk reduction 57 percent. In addition, intensive therapy in those with residual beta cell function resulted in a lower A1C, a 50 percent reduced risk for retinopathy progression, and a lower risk for severe hypoglycemia compared to those who received intensive therapy but did not have residual beta cell function.

CHOICE OF INSULIN REGIMEN — The approximate time of onset, peak activity, and duration of action of the most commonly used insulins are reviewed elsewhere.The choice of regimen is largely a matter of patient and physician preference. The basic requirements are a stable baseline dose of insulin (basal insulin) (whether an intermediate or long-acting insulin or given via continuous subcutaneous insulin infusion) plus adjustable doses of pre-meal short-acting insulin (regular) or rapid-acting insulin analogs (lispro, aspart, or glulisine).

In the DCCT, in which all supplies were free, patients in the intensive therapy group were allowed to choose between multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII) and could switch between the two during the study. Fifty-nine percent of the patients in the intensive therapy group used a pump at least part of the time; however, the pump was used for only 34 percent of the time during the study. Glycemic control, frequency of severe hypoglycemia, and progression of microvascular disease were similar with either type of insulin therapy. Small trials comparing intensive insulin therapy using MDI versus CSII reported similar findings and additionally reported no difference in quality of life measures between treatment groups [6,7].Thus, the major decision in initiating intensive insulin therapy is whether the patient and physician are more comfortable with multiple daily injections or continuous subcutaneous insulin infusions. The choice between multiple daily injection regimens and insulin pump therapy should largely be predicated on patient preference and lifestyle.

Multiple daily injections — In the past, the most commonly used multiple-dose regimen (ie, “conventional insulin therapy”) consisted of twice-daily injections of short-acting (regular) and intermediate-acting insulin. This regimen was based on the concept that each of the four doses is covering one quarter of the day and results in a single peak of insulin absorption. This regimen is not physiologic and is no longer recommended unless the patient cannot or will not comply with an intensive insulin regimen.

Many different insulin regimens may be used to accomplish intensive insulin therapy. Some of the more common ones are shown in the table. The choice of basal and bolus insulins for a multiple daily injection (MDI) regimen depends upon patient preference, lifestyle, and cost concerns. Irrespective of the type of insulin chosen, these intensive insulin regimens should be monitored with frequent blood glucose determinations, at least four times per day.Insulin glargine — Insulin glargine is identical to human insulin except for a substitution of glycine for asparagine in position A21 and by the addition of two arginine molecules in the B-chain of the insulin molecule. These modifications result in a change in the pH such that after subcutaneous administration, glargine precipitates in the tissue forming hexamers, which delays absorption and prolongs duration of action. The time-action profile for insulin glargine has virtually no peak (graph 4), which makes it a good basal insulin preparation for intensive insulin therapy [8-10].The therapeutic advantage of insulin glargine over NPH is modest. In a pooled analysis of trials comparing glargine with NPH in adults with type 1 diabetes, the weighted mean difference in A1C was -0.11 percent (95% CI -0.21 to -0.02), favoring glargine. There was no difference in the number of hypoglycemic episodes. It is unclear whether the modest benefits of glargine compared with NPH merit the added expense and inconvenience of not being able to mix it with other insulins (sometimes requiring an additional injection, when compared with NPH regimens). In addition, long-term safety is unknown.

In patients with type 1 diabetes (but not type 2), glycemic control is similar if once-daily glargine is given before breakfast, before dinner, or at bedtime but there is less nocturnal hypoglycemia with breakfast administration. This was illustrated in a randomized trial of 378 patients with type 1 diabetes who received pre-meal doses of insulin lispro in addition to one of the three glargine regimens. A1C was similar in the three groups, but nocturnal hypoglycemia occurred in 60 percent of patients taking glargine before breakfast, 72 percent before dinner, and 78 percent at bedtime.Although many patients can achieve stable basal serum insulin concentrations with a single daily injection of insulin glargine given in the morning or evening (regimens 3 and 4; this is not always the case. In my experience, about 20 percent of patients with type 1 diabetes need twice-daily glargine. Insulin detemir — Insulin detemir is another available long-acting insulin analog. It is an insoluble molecule with a fatty acid side chain that allows albumin binding, which results in prolongation in action. Insulin detemir is considerably less potent than human insulin and is formulated so that four detemir molecules have roughly the same potency as one molecule of human insulin. Its duration of action appears to be substantially shorter than that of insulin glargine [15], though still longer than NPH (table 1). In one study, a detemir dose of 0.29 units/kg provided the same effect as 0.3 units/kg NPH, but with a longer duration of action (16.9 versus 12.7 hours, respectively) [16]. Like NPH, twice-daily injections appear to be necessary in patients with type 1 diabetes.Glycemic control appears to be similar in trials comparing insulin detemir and NPH. In a pooled analysis of trials comparing detemir with NPH in patients with type 1 diabetes, there was no difference in A1C (weighted mean difference -0.06 percent, 95% CI -0.13 to 0.02). However, insulin detemir was associated with a slightly lower risk of severe hypoglycemia and nocturnal hypoglycemia. These modest advantages of insulin detemir may be offset by its higher cost and unknown long-term safety profile.Rapid-acting insulin — To produce an insulin preparation with a faster onset and shorter duration than regular insulin, modifications have been made in the insulin molecule to prevent it from forming dimers and other complexes that slow absorption and delay action. The resulting rapid-acting insulins (insulin lispro, aspart, and glulisine) have an onset of action within 5 to 15 minutes, peak action at 30 to 90 minutes, and a duration of action of two to four hours.

In patients with type 1 diabetes, rapid-acting insulin has the following advantages when compared to regular insulin [17]:It decreases the postprandial rise in blood glucose concentration.It is more convenient because it can be injected immediately before meals, whereas regular insulin should be given 30 to 45 minutes before meals to optimally match the glycemic excursions after a meal. In addition, the action of insulin lispro is not blunted by mixing with NPH insulin just before injection, as is the action of regular insulin [18].Despite these advantages, the results from clinical trials have been somewhat disappointing [19]. In a meta-analysis of 42 randomized controlled trials (involving 5925 patients with type 1 diabetes) that compared rapid-acting insulin analogues to regular insulin showed only a minor benefit of insulin analogs in terms of A1C values [20].In a subsequent pooled analysis of trials comparing lispro or aspart with regular insulin in patients with type 1 diabetes, the insulin analogs provided a similar small improvement in A1C (weighted mean difference -0.09 to -0.13 percent) [11]. It is unclear if this small improvement will provide clinical benefit. There are few data examining the effects of insulin analogs on long-term diabetic complications. In some [11,21], but not all [18], meta-analyses comparing rapid acting insulin analogs with regular insulin, there was a lower risk of severe hypoglycemia with use of lispro. Although the risk of severe hypoglycemia was not significantly different in a pooled analysis of trials comparing aspart and regular insulin [11], there was a lower risk of hypoglycemia with aspart compared with lispro when the insulin analogs were administered as a continuous subcutaneous insulin infusion [22].The rapid acting insulins are particularly useful in addressing unexpectedly high blood glucose levels (eg, between meals or in the setting of stress) because they will lower glucose levels more rapidly and without the prolonged effect of regular insulin [23-25].One disadvantage of rapid-acting insulins is their higher cost [17]. The teratogenicity and long term safety profile of short-acting insulins in pregnancy are unknown, although many diabetologists do prescribe rapid-acting insulins during pregnancy.Choosing basal/bolus insulin — The choice of basal and bolus insulin for a multiple daily injection regimen depends upon patient preference, lifestyle, and cost concerns. In short-term trials, there may be a modest glycemic benefit of analogs over conventional insulin. However, it is of uncertain clinical significance and long-term trials with diabetic complications as endpoints are lacking.As an example, in an 18-week trial in 595 adults with type 1 diabetes randomly assigned to NPH/regular versus detemir/aspart, there was a small but significant difference in A1C values (mean difference -0.22 percentage points) favoring the insulin analogs.

Richard Graydon, M.D., PhD

Website: http://www.medauthor.com

Dr. Graydon

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