Rethinking A1c goals for type 2 diabetes

“Treat the patient, not the number.” This is a very old and sound medical school teaching. However, when it comes to blood sugar control in diabetes, we have tended to treat the number, thinking that a lower number would equal better health.

Uncontrolled type 2 diabetes (also known as adult-onset diabetes) is associated with all sorts of very bad things: infections, angry nerve endings causing chronic pain, damaged kidneys, vision loss and blindness, blocked arteries causing heart attacks, strokes, and amputations… So of course, it made good sense that the lower the blood sugar, the lower the chances of bad things happening to our patients.

Tracking blood sugar control over time

One easy, accurate way for us to measure a person’s blood sugar over time is the hemoglobin A1c (HbA1c) level, which is basically the amount of sugar stuck to the hemoglobin molecules inside of our blood cells. These cells last for about three months, so, the A1c is thought of as a measure of blood sugars over the prior three months.

Generally, clinical guidelines have recommended an A1c goal of less than 7% for most people (not necessarily including the elderly or very ill), with a lower goal — closer to normal, or under 6.5% — for younger people.

We as doctors were supposed to first encourage diet and exercise, all that good lifestyle change stuff, which is very well studied and shown to decrease blood sugars significantly. But if patients didn’t meet those target A1c levels with diet and exercise alone, then per standard guidelines, the next step was to add medications, starting with pills. If the levels still weren’t at goal, then it was time to start insulin injections.

While all this sounds very orderly and clinically rational, in practice it hasn’t worked very well. I have seen firsthand how enthusiastic attention to the A1c can be helpful as well as harmful for patients.

And so have experts from the Clinical Guidelines Committee of the American College of Physicians, a well-established academic medical organization. They examined findings from four large diabetes studies that included almost 30,000 people, and made four very important (and welcome!) new guidelines around blood sugar control. Here’s the big picture.

Doctors and patients should discuss goals of treatment together and come up with an individual plan

Blood sugar goals should take into account a patient’s life expectancy and general health, as well as personal preferences, and include a frank discussion of the risks, benefits, and costs of medications. This is a big deal because it reflects a change in how we think about blood sugar control. It’s not a simply number to aim for; it’s a discussion. Diabetes medications have many potential side effects, including dangerously low blood sugar (hypoglycemia) and weight gain (insulin can cause substantial weight gain). Yes, uncontrolled blood sugars can lead to very bad things, but patients should get all the information they need to balance the risks and benefits of any blood sugar control plan.

An A1c goal of between 7% and 8% is reasonable and beneficial for most patients with type 2 diabetes…

…though if lifestyle changes can get that number lower, then go for it. For patients who want to live a long and healthy life and try to avoid the complications of diabetes, they will need to keep their blood sugars as normal as possible — that means an A1c under 6.5%. However, studies show that using medications to achieve that goal significantly increases the risk of harmful side effects like hypoglycemia and weight gain. To live longer and healthier and avoid both the complications of diabetes as well as the risks of medications, there’s this amazing thing called lifestyle change. This involves exercise, healthy diet, weight loss, and not smoking. It is very effective. Lifestyle change also can help achieve healthy blood pressure and cholesterol levels, which in turn reduce the risk for heart disease. And heart disease is a serious and common complication of diabetes.

Lifestyle change should be the cornerstone of treatment for type 2 diabetes. The recommendations go on to say that for patients who achieve an A1c below 6.5% with medications, we should decrease or even discontinue those drugs. Doing so requires careful monitoring to ensure that the person stays at the goal set with his or her doctor, which should be no lower than 7%, for the reasons stated above.

We don’t even need to follow the A1c for some patients

Elderly patients, and those with serious medical conditions, will benefit from simply controlling the symptoms they have from high blood sugars, like frequent urination and incontinence, rather than aiming for any particular A1c level. Who would be included in this group? People with a life expectancy of less than 10 years, or those who have advanced forms of dementia, emphysema, or cancer; or end-stage kidney, liver, or heart failure. There is little to no evidence for any meaningful benefit of intervening to achieve a target A1c in these populations; there is plenty of evidence for harm. In particular, diabetes medications can cause low blood sugars, leading to weakness, dizziness, and falls. There is the added consideration that elderly and sick patients often end up on a long list of medications that can (and do) interact, causing even more side effects.

The bottom line

There is no question that type 2 diabetes needs to be taken seriously and treated. But common sense should rule the day. Lifestyle changes are very effective, and the side effects of eating more healthfully and staying more active are positive ones. Every person with type 2 diabetes is an individual. No single goal is right for everyone, and each patient should have a say in how to manage their blood sugars and manage risk. That means an informed discussion, and thoughtful consideration to the number.

Sources

Hemoglobin A1c targets for glycemic control with pharmacologic therapy for nonpregnant adults with type 2 diabetes mellitus: A guidance statement update from the American College of Physicians. Annals of Internal Medicine, March 2018.

An overview of the management of diabetes in non-pregnant adults. MGH Primary Care Office Insite, updated June 2016.

Management of persistent hyperglycemia in type 2 diabetes mellitus. UpToDate, updated April 2017.

Ways to Lower Your A1C

For some, home blood sugar testing can be an important and useful tool for managing blood sugar on a day-to-day basis. Still, it only provides a snapshot of what’s happening in the moment, not the full picture of what’s happened in the long term, says Gregory Dodell, MD, an assistant clinical professor of medicine, endocrinology, diabetes, and bone disease at Mount Sinai in New York City.

For this reason, your doctor may occasionally administer a blood test that measures your average blood sugar level over the past three months. Called hemoglobin A1C, or A1C, this test can show you how well your type 2 diabetes management plan is working.

Here’s what you should know about it and ways to make sure your A1C is in a healthy range.

   Poll

How often do you get your A1C tested?

How Often Do You Need to Take an A1C Test?

If your blood sugar levels have remained stable and your A1C is within your target range, the American Diabetes Association (ADA) recommends getting the test two times a year. If your therapy has changed or you are not meeting your blood sugar targets, the ADA recommends getting the test four times per year. This simple blood draw can be done in your doctor’s office.

The A1C test results provide insight into how your treatment plan is working and how it might be modified to better control the condition. Often, your blood sample is sent out to a lab, though some doctors can use a point-of-care A1C test, where a finger stick can be done in the office, with results available in about 10 minutes.

While in-office tests can be used to monitor the disease, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) notes that most point-of-care tests should not be used for diagnosis. That can only be done by lab tests certified by the NGSP, an organization that standardizes A1C test results. Any in-office test results pointing to a change in your health should be confirmed by conventional lab tests.

What Do Your A1C Results Mean?

The A1C test measures the glucose (blood sugar) in your blood by assessing the amount of what’s called glycated hemoglobin. “Hemoglobin is a protein within red blood cells. As glucose enters the bloodstream, it binds to hemoglobin. The more glucose that enters the bloodstream, the higher the amount of glycated hemoglobin,” Dr. Dodell says.

According to the ADA, an A1C level below 5.7 percent is considered normal; between 5.7 and 6.4 signals prediabetes; and over 6.5 percent indicates type 2 diabetes. For many people with type 2 diabetes, the goal is to reduce A1C levels.

Your A1C goal is specific to you. Several factors come into play, such as your age, how advanced the diabetes is, and whether you have any other health conditions. If you can keep your A1C number below your goal — which, for many people with diabetes, is less than 7 percent, says Dodell — you can reduce the risk of complications, such as nerve damage and eye problems.

What Are Some Top Tips for Lowering A1C?

Your A1C score is a helpful tool, Dodell says, but it is not the only indicator of how healthy you are.

For example, you could hit your A1C goal but still have wide fluctuations in your blood sugar levels, which is more common among people who take insulin. You’ll need to bring these day-to-day fluctuations under control, since they can lower your quality of life and increase your risk of complications, he says.

Think of your diabetes as you would a job, Dodell says. It takes work, but the time and effort you put into it can result in good control and an improved quality of life. “The key to reaching your A1C goal is trying to follow a healthy lifestyle,” he says.

Making these changes can help you improve your day-to-day blood sugar management and lower your A1C.

1. Start an Exercise Plan You Enjoy, and Do It Regularly

Find something you enjoy doing that gets your body moving, whether it’s taking your dog for a walk, playing a sport with a friend, or riding your bike.

The ADA recommends getting 150 minutes of moderate exercise per week, says Jordana Turkel, a certified diabetes care and education specialist (CDCES) and registered dietitian at Park Avenue Endocrinology & Nutrition in New York City. Different types of exercise (both strength or resistance training and aerobic exercise) can lower your A1C by making your body more sensitive to insulin, Turkel says. She encourages her patients not to go more than two days in a row without exercising and to aim for two days of strength training per week.

Be sure to check with your healthcare provider before embarking on an exercise plan, though. Together, you can come up with an individualized plan.

And if you monitor your blood sugar daily, check it before and after exercise. As the ADA explains, exercise improves insulin sensitivity and lowers your blood sugar levels. In certain circumstances, though, stress hormones produced during more intense exercise can also increase blood sugar levels. In addition, other factors, such as what you eat before exercise and the timing of your workout, may also affect your numbers.

2. Eat a Balanced Diet With Proper Portion Sizes

It’s best to check with a CDCES or registered dietitian/nutritionist to determine what a balanced diet and appropriate portion sizes mean for you. But a great rule of thumb is to fill half of your plate with veggies, a quarter with protein, and a quarter with whole grains, says Turkel. If you like fruit, limit your portion to a small cup, eaten with a little protein or lean fat to help you digest the carbohydrates in a way that is less likely to spike your blood sugar.

Also, avoid processed foods as much as possible, and try to avoid sugary sodas and fruit juice, which are high in carbs and calories, and thus can lead to spikes in blood sugar and contribute to weight gain, according to the ADA.

3. Stick to a Regular Schedule, So You Can More Easily Follow a Healthy Diet 

Skipping meals, letting too much time pass between meals, or eating too much or too often can cause your blood sugar levels to fall and rise too much, Cleveland Clinic points out. This is especially true if you are taking insulin or certain other diabetes drugs. Your doctor can help you determine the best meal schedule for your lifestyle.

4. Follow the Diabetes Treatment Plan Your Healthcare Team Recommends

Diabetes treatment is very individualized, noted a February 2022 article in Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy. After all, factors including how long you’ve lived with the disease, your socioeconomic status, and any other conditions you’re living with can play a role in the best treatment approach for you.

Your healthcare team will help you determine which steps to take to successfully manage diabetes. Always talk to your doctor before making any changes, such as starting a diet very low in carbohydrates or beginning a new exercise regimen. This is especially important before making any medication or insulin changes.

5. Check Your Blood Sugar Levels as Your Doctor Has Directed

Work with your doctor to determine if you should check your blood sugar — and how often. You may be tempted to pick up an A1C home testing kit, but Dodell says having your A1C checked by your doctor every three to six months is sufficient. A better idea is to use a continuous glucose monitor. He recommends checking your “time in range” to see if you are at the optimal level. For many people that is 70 to 180 milligrams per deciliter (3.9 to 10 millimoles per liter), according to ADA guidelines.

Understanding your A1C levels is an important part of your overall diabetes management. If you have any questions about your A1C or what it means, don’t hesitate to ask your doctor.

Additional reporting by Mikel Theobald

Modern strategy of hypoglycemic therapy in type 2 diabetes mellitus: the role and place of combination therapy | Nedosugova L.

V.

The spread of type 2 diabetes mellitus (T2DM) in the world exceeds all theoretical forecasts. If 15 years ago, WHO experts assumed that by 2025 the number of patients with diabetes in the world would be 380 million people [1], then, according to the International Diabetes Association (IDF), in 2011 the number of patients with diabetes has already reached 366 million, and , according to WHO experts, by 2030 the number of patients with T2DM will be 552 million people [2]. Life expectancy in patients with T2DM is on average 5 years shorter than in the general population, and this is primarily due to the rapid progression of atherosclerosis, which leads to cardiovascular mortality in T2DM patients 4–5 times more often [3]. Overall, more people with diabetes die from atherosclerosis-related diseases than from all other causes combined [4]. The cause of such a pronounced lesion of the vascular bed is currently considered to be hyperglycemia. Meta-analysis of 20 different studies including 95,783 patients followed up for 12 years led to the conclusion that glucose is the same risk factor for the development of atherosclerosis and acute cardiovascular mortality as the level of total cholesterol and blood pressure [5].

A series of large randomized trials [6-10] have proven the importance of tight glycemic control in reducing the risk of developing diabetic vascular complications, which requires aggressive treatment of T2DM using effective and safe hypoglycemic drugs and their combinations already at the diagnosis of the disease, allowing to achieve the target level of glycemia, which, as proven by long-term observations, can prevent the rapid progression of atherosclerosis in these patients [11, 12].
However, the intensification of hypoglycemic therapy is limited by the risk of developing hypoglycemic conditions, weight gain and, as a result, increased mortality from acute vascular accidents. Hypoglycemic episodes were 3 times more common in the intensive care group compared with standard therapy in the ACCORD study [13] and 2 times more often in the VADT study [14], which was accompanied by a 22% increase in overall mortality in the ACCORD study and an increase in cases cardiovascular events in the next 3 months. after severe hypoglycemia in the elderly in the VADT study.
In connection with the above, at the end of 2011, the Russian Association of Endocrinologists proposed to individualize the target levels of glycemic control [15] depending on the patient’s age, life expectancy (LE), the risk of developing hypoglycemic conditions, and the presence/absence of severe cardiovascular complications (Table 1). 1).
T2DM is characterized by two major pathogenetic defects: decreased insulin sensitivity (or insulin resistance) and inadequate insulin secretion to overcome the barrier of insulin resistance. Insulin resistance often precedes the development of DM for many years and is genetically determined, although exacerbated by external factors such as obesity, decreased physical activity, pregnancy, and excess contrainsular hormones. Initially, existing insulin resistance is compensated by hyperinsulinemia, which maintains normal carbohydrate tolerance. Impaired carbohydrate tolerance is observed with an increase in insulin resistance or a decrease in the compensatory capabilities of insulin secretion, or with the progression of both defects [16, 17]. According to modern concepts, T2DM manifests itself in a situation where the secretory capabilities of β-cells are unable to overcome the barrier of insulin resistance. The main role in this failure of the insular apparatus is assigned to genetic disorders [17], however, the so-called “glucose toxicity phenomenon” plays an important role in reducing the secretory reserves of the insular apparatus, due to which apoptosis and death of β-cells develop. According to statistics, by the time of the disease manifestation, only 50% of the initial number of β-cells are functioning in patients, which confirms the theory of the gradual progression of carbohydrate metabolism disorders: from normoglycemia in conditions of insulin resistance and hyperinsulinemia to the manifestation of diabetes through successive stages of impaired fasting glycemia and impaired tolerance to glucose [18].
Based on the foregoing, a completely logical conclusion suggests itself that the main strategic direction in the treatment of T2DM should be the impact on insulin resistance as the main pathogenetic link in the development of the disease. By reducing insulin resistance, or, in other words, increasing insulin sensitivity, we reduce the load on the insular apparatus, thereby preserving its secretory capabilities and removing the negative effect of hyperinsulinemia on increased appetite, weight gain, and the state of the cardiovascular system. The easiest way to increase insulin sensitivity is to reduce weight through lifestyle and dietary changes, which, unfortunately, allows achieving the target level of glycemia in less than 30% of patients with newly diagnosed T2DM [6]. In such situations, agents are needed that affect the main pathogenetic link of the syndrome – insulin resistance.
Currently, the most accessible and effective drug is metformin (the original metformin drug is Glucophage®), the main mechanism of action of which is to reduce insulin resistance by increasing the activity of the insulin receptor tyrosine kinase in peripheral tissues. As a result, the utilization and oxidation of glucose in peripheral tissues improves [19, 20], and lipolysis and oxidation of free fatty acids as an alternative energy substrate are suppressed [21, 22]. It is with an increase in insulin sensitivity of the liver tissue that a decrease in gluconeogenesis and glycogenolysis is associated [23, 24]. Thus, the hypoglycemic effect of metformin is not so much hypoglycemic as antihyperglycemic, because. leads to a decrease in hepatic glucose production and fasting glucose levels. An increase in the sensitivity of peripheral tissues to insulin is also associated with a decrease in the need for insulin and an improvement in the functionality of β-cells due to a decrease in glucose toxicity [25]. In addition, as recent studies show, metformin can increase the level of glucagon-like peptide-1 (GLP-1), which, as you know, stimulates insulin secretion by improving glucose absorption in the more distal parts of the small intestine, where L-cells are mainly localized. secreting GLP-1 [26].
In case of metformin intolerance or contraindications, the latest 2011 IDF algorithm suggests, as an alternative option for patients who are not overweight, the use of sulfonylurea drugs (SUM) as the first line of treatment, based on the assumption that the main pathogenetic defect in the development of T2DM without obesity is inadequate secretion of insulin. This option of starting drug treatment is justified not only by the need for a pathogenetic approach to therapy, but also by a sufficient evidence base for the effectiveness and safety of the use of PSM, as well as the relative cheapness and availability of such an alternative treatment option.
As noted above, in the majority of people with T2DM, lifestyle interventions fail to achieve target carbohydrate metabolism, either due to inadequate weight loss, weight gain, disease progression, or a combination of these and other factors. Therefore, it is recommended to start metformin therapy along with lifestyle changes immediately after diagnosis. In the absence of specific contraindications, metformin is recommended primarily due to its effect on glycemia, lack of weight gain and hypoglycemic conditions, generally good tolerability with a low incidence of side effects, high adherence, and relatively low cost. The dose of metformin should be gradually (over 1-2 months) increased to the maximum effective and tolerated.
Second line therapy
At the same time, even the maximum doses of metformin do not always make it possible to achieve the target level of glycemia and reduce the level of Hb A1c <7.0% during the first 2–3 months. treatment as recommended by the authors of the latest IDF algorithm (2011). If persistent hyperglycemia persists, the question of the rapid addition of other hypoglycemic drugs should be addressed. A clear consensus on a second drug added to metformin does not yet exist, and the choice is between SSM and DPP-4 or TZD inhibitors and α-glucosidase blockers as an alternative (Fig. 1). In particular, when the risk of hypoglycemia is especially dangerous (for example, in patients engaged in heavy physical labor), it is advisable to additionally prescribe DPP-4 inhibitors or the TZD class of drugs - pioglitazone. In cases where one of the main goals of treatment is weight loss, and the level of Hb A1c is <8.0%, it is preferable to prescribe α-glucosidase blockers.
As a second line of drugs, if it is impossible to achieve the target level of glycemic control with the use of SSM, the use of metformin is suggested, if it has not been previously prescribed, or DPP-4 inhibitors, or TZD, or α-glucosidase blockers as an alternative option (Fig. 1).
Third line therapy
If lifestyle modification, metformin, and the second drug did not lead to the achievement of the target parameters of carbohydrate metabolism control, the next step is to start or intensify insulin therapy (Fig. 1). If the A1c level is close to the target (< 8.0%), a third oral antidiabetic drug can be added as an alternative. As an additional hypoglycemic agent, the 2011 IDF algorithm suggests either α-glucosidase blockers or DPP-4 inhibitors, or TZD, or, as an alternative, GLP-1 agonists (exenatide, liraglutide) when one of the main goals of treatment is to reduce weight, and the level of Hb A1c <8.0%. However, this approach is more expensive and not always effective compared to switching to insulin therapy or its intensification.
Fourth line therapy
Intensive insulin therapy usually consists of additional injections of short-acting or ultra-rapid-acting insulin before individual meals to reduce postprandial glycemic fluctuations (Fig. 1). When switching to intensive insulin therapy with short-acting or rapid-acting insulin injections, insulin secretogens (PSM or glinides) should be discontinued, since they have a synergistic effect with injected insulin.
However, endocrinologists often face the problem of not being able to achieve the target level of glycemic control within 2-3 months. treatment. This is due to the fact that the initial level of Hb A1c in patients can range from 6.5 to 10% or more, which, of course, complicates the ability to quickly and effectively achieve the goal.
Stratification of treatment tactics
according to the Algorithm of the RAE 2011
In this regard, the Russian Association of Endocrinologists (RAE) at the end of 2011 proposed a differentiated approach to prescribing and correcting hypoglycemic therapy depending on the initial level of Hb A1c, followed by a change in treatment if the goal is not achieved no earlier than after 6 months. from the start of therapy. Indeed, if the initial level of Hb A1c does not exceed 7.5%, it is quite possible to achieve the target level of <6.5% with monotherapy with metformin, pioglitazone, DPP-4 inhibitors (dipeptidyl peptidase) or α-glucosidase, as shown in Figure 2. A double combination in case of ineffective monotherapy involves the addition of drugs that somehow stimulate insulin secretion either due to a direct effect on the β-cell (PSM, glinides and GLP-1 analogues), or indirectly, due to blockade of the cleavage of native GLP-1 by inhibitors of the DPP-enzyme. 4. In any case, this combination affects both pathogenetic links in the development of T2DM: insulin resistance and inadequate secretion of insulin, resulting in adequate glycemic control not only in terms of fasting glycemia, but also after meals, leading to rapid achievement of the goal.
Which combination is preferred in patients with baseline Hb A1c between 6.5% and 7.5%? Based on the tolerability and safety criteria, the possible risk of hypoglycemia when using secretogens in patients with initially low levels of Hb A1c exceeds the severity of side effects from the gastrointestinal tract and edematous syndrome associated with the use of incretins and TZD, respectively. That is why the authors of the RAE algorithm suggest, first of all, the combination of metformin with DPP-4 inhibitors or GLP-1 analogues, and secondly, metformin with secretogens (PSM or glinides), as the most rational combinations. If lifestyle modification, metformin, and the second drug did not lead to the achievement of the target parameters of carbohydrate metabolism control, the next step is to start or intensify insulin therapy (Fig. 2). If the A1c level is close to the target (<7.5%), a third oral hypoglycemic agent can be added. However, this approach is more expensive and not always effective compared to switching to insulin therapy or its intensification [27].
Case Management
with A1c level from 7.6 to 9%
The vast majority of patients with T2DM have an A1c level of >7.6% at the time of disease diagnosis. To date, there are no drugs that can achieve the target level of control in monotherapy for 2-3 months. (Table 2).
That is why the authors of the algorithm propose to initially use combined “double” therapy to achieve rapid and effective glycemic control (Fig. 3). This approach is based on the data of numerous studies showing that the simultaneous administration of drugs with different points of application of action provides a more significant decrease in A1c not only in a shorter time, but also at significantly lower dosages than the initial metformin monotherapy followed by the addition of a second drug [28– thirty]. Metformin is the basis of all possible combinations, of which the combination of metformin with incretin mimetics is the safest, due to the absence of the risk of hypoglycemic conditions and weight gain, and the most effective is the combination of metformin with PSM, since these drugs most significantly reduce the level of A1c, and their combination provides good control not only of glycemia, but also of cholesterol and blood lipid spectrum [30].
In case of ineffectiveness of “dual” therapy, it is recommended to add a third drug, based on the principles of efficiency and safety in this case: Metformin is considered the basis of therapy in this situation, while the safest in terms of the risk of developing hypoglycemic conditions is the addition to the combination of metformin with incretin TZD mimetics, and the most effective is the addition of PSM to a combination of metformin with incretin mimetics. Thus, in patients with A1c levels close to 7.5%, it is more appropriate to prescribe a combination of metformin with TZD and incretin mimetics, while in patients with higher A1c levels, it is more logical to use a combination of metformin with SM and incretin mimetics. The next step in achieving the target level of glycemia with the ineffectiveness of the “triple” combination is the appointment of insulin therapy, first in the background, and then in the background-bolus mode, upon transition to which it is necessary to cancel drugs that somehow stimulate insulin secretion.
Case Management
at A1c >9%
In clinical practice, situations are not uncommon in which, already at the stage of T2DM diagnosis, patients have significant hyperglycemia and the Hb A1c level exceeds 9%, but there are no clinical symptoms of the disease, which indicates sufficient secretory activity of the insular apparatus. The tactics of choice in this situation, at the suggestion of the authors of the algorithm, may not be intensive insulin therapy, which is absolutely indicated for A1c > 10% and severe clinical symptoms, but the initial “triple” therapy. In this case, the combination of metformin with PSM and incretin mimetics is considered the most effective, the most safe in terms of the risk of hypoglycemia is the combination of metformin with incretin mimetics and TZD (Fig. 4).
However, practitioners are well aware of the adverse effect of complex hypoglycemic regimens on patient adherence to medical prescriptions in daily practice. According to the results of the DARTS study [31], only 30% of patients are firmly adherent to single-drug therapy and less than 13% adhere to multiple drugs and high doses (separate combination). It is this fact that explains the emergence of official combined hypoglycemic drugs, consisting of a combination of metformin with various drugs of other classes. The most effective is the combination of metformin with PSM, which allows to achieve the most rapid and significant decrease in the level of A1c, while using smaller doses of each of the components, which, of course, reduces the risk of development and severity of side effects (gastrointestinal disorders, weight gain, hypoglycemic conditions) .
One of the drugs of this group, registered in Russia, is Glyukovance®, the only combination drug in Russia that contains the original metformin and glibenclamide in a micronized form, which provides a number of advantages compared to the usual form of glibenclamide, confirmed in clinical trials, including: hours, lower risk of hypoglycemia and safer action compared to the conventional form of glibenclamide [28, 33]. In addition, the faster release of glibenclamide from the Glucovance® tablet is more effective in preventing an increase in glycemia in the first 3 hours after a meal compared to the standard form of glibenclamide [34, 35]. The calibrated particle size technology used in the creation of Glucovance® provides controlled release of drug components in accordance with the physiological needs of the patient [34]. Thus, the target values ​​of glycemia are achieved with the use of lower doses of metformin and glibenclamide in the composition of Glucovance® in comparison with the doses used in monotherapy [33].
The drug is available in two dosages containing 2.5/500 mg of glibenclamide/metformin and 5.0/500 mg of glibenclamide/metformin, respectively, which makes it possible to titrate the dose of glibenclamide to reduce the risk of developing hypoglycemic conditions. Thus, using Glucovance in the treatment of T2DM, it is possible to achieve the target level of glycemic control both in patients with ineffectiveness of higher doses of metformin or in case of its intolerance, and in patients who are initially indicated for “double” therapy with A1c> 8.0% or ” triple” therapy at the level of A1c> 90% in combination with incretin mimetics or TZD. The use of Glucovans not only provides an effect on both major pathogenetic defects in T2DM, but also allows to achieve an effect at lower doses with a lower risk of side effects and with greater patient compliance with the prescribed therapy [36]. Glucovance can be used in any cohort of patients with T2DM, regardless of the initial HbA1c level, of course, taking into account individual treatment goals that exclude the risk of developing hypoglycemic conditions, in the absence of severe vascular complications, taking into account age and life expectancy.

Literature
1. World Health Organization: “The World Health Report 1998. Life in the 21st Century – a Vision for ALL”. – Geneva: World Health Organization, 1998.
2. Suntsov Yu.I. Modern hypoglycemic drugs used in Russia in the treatment of type 2 diabetes // Sakh. diabetes. 2012. No. 1. S. 6–10.
3. Hsueh W.A., Law R.E. Cardiovascular risk continuum: Implications of insulin resistance and diabetes // Am. J. Med. 1998 Vol. 105.4S-14S.
4. Dobordzhginidze L.M., Gratsiansky N.A. The role of statins in the correction of diabetic dyslipidemia // Sakh. diabetes. 2001. No. 2. C.41–47.
5. Coutinho M., Gerstein H.C., Wang Y., Yusuf S. The relationship between glucose and incident cardiovascular events: a metaregression analysis of published data from 20 studies of 95,783 individuals followed for 12.4 years // Diabetes Care. 1999 Vol. 22. P. 233–240.
6. UK Prospective Diabetes Study (UKPDS) Group: Intensive blood glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complication in patients with type 2 diabetes (UKPDS 33) // Lancet. 1998 Vol. 352. P. 837–853.
7. Ohkubo Y., Kishikawa H., Araki E. et al. Intensive insulintherapy prevents the progression of diabetic microvascular complications in Japanese patients with NIDDM: a randomized prospective 6-year study // Diabetes Res. Clin. Pract. 1995 Vol. 28. P. 103–117.
8. Kahn S.E., Zinman B., Lachin J.M. et al. A Diabetes Outcome Progression Trial [ADOPT] Study Group. Rosiglitazone-associated fractures in type 2 diabetes:an analysis from A Diabetes Outcome Progression Trial (ADOPT) // Diabetes Care. 2008 Vol. 31. P. 845–851.
9. Patel A., MacMahon S., Chalmers J. et al. ADVANCE Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes // N. Engl. J. Med. 2008 Vol. 358. P. 2560–2572.
10. Wilcox R., Kupfer S., Erdmann E. PROactive Study Investigators. Effects of pioglitazone on major adverse cardiovascular events in high-risk patients with type 2 diabetes: results from PROspective pioglitAzone Clinical Trial In macro Vascular Events (PROactive 10) // Am. Heart J. 2008. Vol. 155. P. 712–717.
11. Holman R.R., Paul S.K., Bethel M.A. et al. 10-year follow-up of intensive glucose control in type 2 diabetes // N. Engl. J. Med. 2008 Vol. 359. P. 1577–1589.
12. Gaede P., Valentine W.J., Palmer A.J. et al. Costeffectiveness of intensified versus conventional multifactorial intervention in type 2 diabetes: results and projections from the Steno-2 study // Diabetes Care. 2008 Vol. 31. P. 1510–1515.
13. Miller M.E., Byington R.P., Goff D.C. Jr et al. Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive glucose lowering in type 2 diabetes // N. Engl. J. Med. 2008 Vol. 358. P. 2545–2559.
14. Duckworth W., Abraira C., Moritz T. et al. VADT Investigators. Glucose control and vascular complications in veterans with type 2 diabetes [published correction appears] // N. Engl. J. Med. 2009 Vol. 361. P. 1024–1025, 1028], N. Engl. J. Med. 2009 Vol. 360. P. 129–139.
15. Algorithms for specialized medical care for patients with diabetes mellitus / Ed. I.I. Dedova, M.V. Shestakova. – M .: LLC “Informpolygraph”, 2011. 115 p.
16. DeFronzo R.A. Pathogenesis of type 2 diabetes: metabolic and molecular implications for identifying diabetes genes // Diabetes Rev. 1997 Vol. 5. P. 177–269.
17. Kahn C.R., Vicent D., Doria A. Genetics of non-insulin-dependent (type-II) diabetes mellitus, Ann. Rev. Med. 1996 Vol. 47. P. 509–531.
18. Kahn C.R. Insulin action, diabetogenes, and the cause of type II diabetes // Diabetes. 1994 Vol. 43. P. 1066–1084.
19. Kirpichnikov D., McFarlane S.I., Sowers J.R. Metformin: an update // Ann. Intern. Med. 2002 Vol. 137. P. 25–33.
20. Riccio A., Del Prato S., Vigili de Kreutzenberg S., Tiengo A. Glucose and lipid metabolism in non-insulin-dependent diabetes. Effect of metformin // Diabetes. Metab. 1991 Vol. 17. P. 180–184.
21. Perriello G., Misericordia P., Volpi E et al. // Acute antihyperglycemic mechanisms of metformin in NIDDM. Evidence for suppression of lipid oxidation and hepatic glucose production // Diabetes. 1994 Vol. 43. P. 920–928.
22. Radziuk J., Zhang Z., Wiernsperger N., Pye S. Metformin and its liver targets in the treatment of type 2 diabetes // Curr. drug. Targets Immune Endocrin. Metabol. Discord. 2003 Vol. 3. P. 151–169.
23. Wollen N., Bailey C.J. Inhibition of hepatic gluconeogenesis by metformin. Synergism with insulin // Biochem. Pharmac. 1988 Vol. 37. P. 4353–4358.
24. Ferner R.E., Rawlins M.D., Alberti K.G.M.M. Impaired B-cell responses improve when fasting blood glucose concentrate is reduced in noninsulin-dependent diabetes // Quat. J. Med. 1988 Vol. 250. P. 137–146.
25. Lindsay J.R., Duffy N.A., McKillop A.M. et al. // Inhibition of dipeptidyl peptidase IV activity by oral metformin in Type 2 diabetes // Diabet. Med. 2005 Vol. 22. P. 654–657.
26. Sinha Roy R., Bergeron R., Zhu L. et al. // Metformin is a GLP-1 secretagogue, not a dipeptidyl peptidase-4 inhibitor // Diabetol. 2007 Vol. 50 (Suppl. 1). S.284.
27 Schwartz S. et al. Insulin 70/30 mix plus metformin versus triple oral therapy in the treatment of type 2 diabetes after failure of the two oral drugs // Diabetes Care. 2003 Vol. 26. P. 2238–2243.
28. De Fronzo R.A., Godman A.M. And The Multicenter Metformin Study Group. Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus // N. Engl. J. Med. 1995 Vol. 333. P. 541–549.
29. Hermann L.S., Schersten B., Bitsen P.-O. et al. Therapeutic comparison of metformin and sulphonylurea alone and in various combinations // Diabetes Care. 1994 Vol. 17. P. 1100–1109.
30. Tosi F., Muggeo M., Brun E. et al. Combination treatment with metformin and glibenclamide versus single-drug therapies in type 2 diabetes mellitus: a randomized, double-blind, comparative study // Metabolism. 2003 Vol. 7. P. 862–867.
31. Morris A.D. Considerations in assessing effectiveness and costs of diabetes care: lessons from DARTS // Diabetes Metab. Res. Rev. 2002 Vol. 18 (Suppl. 3). S.32–35.
32. Nathan D.M., Buse J.B., Davidson M.B. et al. Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy // Diabetes Care. 2006 Vol. 29. P. 1963–1971.
33 Marre M. et al. diabetes. Med. 2002 Vol. 19(8): P. 673–80.
34 Howlett H. et al. Curr. Med. Res. Opin. 2003 Vol. 19(3): P. 218–25.
35. Donahue. Clinical Pharmacokinetics. 2002 (41) 15. P. 1301–1309.
36. Pan F., Chernew M.E., Fendrick A.M. Impact of fixed-dose combination drugs on adherence to prescription medications // J. Gen. Intern. Med. 2008 Vol. 23(5). P. 611–614.

Diabetes Diagnosis – Clinic of Dr. Esipova

Diabetes Diagnosis, biochemical complex includes parameters for assessing carbohydrate metabolism for the purpose of primary detection of diabetes mellitus and differential diagnosis of type 1 and type 2 diabetes.

• What is determined in this study?
• In what cases is the Diabetes Diagnosis, Biochemical complex prescribed?
• What do the test results mean?
• Timing of the test.
• How to prepare for the analysis?

What is determined in this study?

Glucose is the main laboratory test in diagnosing diabetes; the glucose level is noted strictly at the current moment, the influence of various factors is possible. It is used for screening of diabetes mellitus, dynamic monitoring and evaluation of the effectiveness of treatment. An increase in blood sugar is called hyperglycemia, a decrease is called hypoglycemia.

Glycated hemoglobin A1c – an irreversible compound of glucose with hemoglobin, reflects the state of carbohydrate metabolism for about 3 months, which allows you to confirm the presence and degree of increased blood glucose levels, identify “hidden” forms of diabetes and diabetes in pregnant women. The optimal indicator for controlling the course of diabetes mellitus.

Insulin is the main regulator of carbohydrate metabolism. In type 1 diabetes, there is an absolute deficiency of insulin. Type 2 diabetes develops against the background of insulin resistance, when insulin is often elevated. It is not an absolute criterion in the diagnosis of diabetes; it can be falsely changed against the background of insulin therapy.

C-peptide is a fragment of the precursor of insulin, has no biological activity, but is an absolute indicator of the body’s ability to produce insulin, which makes it possible to evaluate insulin secretion during insulin therapy. In type 1 diabetes, its level is reduced.

Insulin antibodies (IAA) is the earliest marker of type 1 diabetes. They are detected before the onset of clinical manifestations, which makes it possible, with aggravated heredity, to identify a predisposition to diabetes.

Pancreatic beta cell antibody (ICA) is a marker of type 1 diabetes. Beta cells or islet cells produce insulin and proinsulin. Relevant for the diagnosis of pregnant women at risk of developing diabetes. In type 2 diabetes, the appearance of these antibodies indicates the risk of impaired ability of the pancreas to produce insulin.

When is Diabetes Diagnosis, Biochemical complex prescribed?

• hyperglycemia detected in children under 10 years of age
• with aggravated heredity in order to identify predisposition to diabetes or diagnose the disease in the early stages
• as part of a comprehensive examination and differential diagnosis of type 1 and type 2 diabetes
• examination of patients with suspected latent course of diabetes

What do the test results mean?

Glucose according to WHO guidelines (1999-2013), Diagnostic criteria for diabetes mellitus and other glycemic disorders:

• Normal fasting glucose: < 6.