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The traditional approach to the treatment of patients with hypertension is to initially prescribe monotherapy with an antihypertensive drug, titrating the dose to the most effective, then adding a second and third drug. However, this approach is quite long and not always effective. In the process of accumulating clinical experience in the treatment of hypertension, it became obvious that monotherapy is effective in only 50% of patients and only with a moderate increase in blood pressure. Often, the development of hypertension involves various pathogenetic mechanisms, and therefore monotherapy cannot have an effect on all causes of increased blood pressure in each individual patient.

In addition, achieving target blood pressure values ​​(< 140/90 мм рт. ст. для лиц без СД и < 130/80 мм рт. ст. для больных СД) требует назначения максимально эффективных доз препарата. Однако при увеличении дозы лекарственного средства возрастает не только его эффективность, но и побочное действие. Дозозависимость побочных эффектов лекарств не позволяет увеличивать их дозу до максимально эффективной. Так, при увеличении дозы традиционных антигипертензивных средств, таких как тиазидные диуретики и ББ, достоверно возрастает риск СД типа 2.

In diabetes, achieving target blood pressure values ​​is an extremely difficult task. The development of hypertension in diabetes is always determined by several mechanisms: hyperactivity of the RAS, an increase in blood volume, activation of the sympathoadrenol system, etc., therefore, monotherapy for patients with diabetes with hypertension is practically ineffective. Meanwhile, exceeding the target blood pressure level threatens the rapid progression of vascular complications. Despite this, only a small number of patients with diabetes receive combination antihypertensive therapy. Thus, an outpatient screening of more than 300 patients with type 1 and type 2 diabetes with varying severity of hypertension, carried out at the State Research Center of the Russian Academy of Medical Sciences in 2002, showed that only 13% of patients had combination therapy for hypertension, and 15% did not receive the necessary treatment at all.

Multicenter clinical randomized studies indicate that to achieve target blood pressure values, the prescription of 2 to 4 drugs of different groups is required.

The advantages of combination therapy for hypertension over monotherapy are obvious:
. combination therapy allows you to influence several mechanisms of the development of hypertension, which makes it more effective;
. combination therapy allows the use of lower doses of prescribed drugs without compromising the antihypertensive effect;
. Some drug combinations eliminate (or reduce) the side effects of individual components.

According to the 2003 recommendations of the VII US Joint National Committee on the Prevention and Treatment of Arterial Hypertension (JNC 7), combination therapy should be prescribed to any patient whose blood pressure exceeds 20/10 mmHg. Art. target values, i.e. 140/90 mmHg. Art. in patients without diabetes and 130/80 mmHg. Art. in patients with diabetes.

A strategy for selecting antihypertensive therapy for patients with diabetes is presented.

Monotherapy is possible only with a moderate increase in blood pressure > 130/80 mm Hg. Art., but< 140/90 мм рт. ст. Препаратами 1-го ряда выбора для больных СД как типа 1, так и 2, являются блокаторы РАС (иАПФ или АРА), поскольку именно эти две группы препаратов обладают максимальными органопротективными (в первую очередь, нефропротективными) свойствами. Если монотерапия блокаторами РАС в эффективных дозах не привела к достижению целевого уровня АД, то наиболее оправдано добавить диуретик, выбор которого зависит от сохранности азотвыделительной функции почек: при отсутствии ХПН можно добавить тиазиды, при наличии ХПН — «петлевые» диуретики.

In some cases, you can prescribe a fixed combination of drugs consisting of an ACE inhibitor or ARB and a thiazide diuretic in low doses (for example: Korenitek = enalapril (Renitec) + hypothiazide ENAP N and ENAP HL = enalapril (ENAP) + hypothiazide, fozide = fosinopril (Monopril) + hypothiazide, gizaar - losartan (cozaar) + hypothiazide. If this combination is ineffective, it is recommended to add a 3rd drug, the choice of which depends on which complication of diabetes is dominant. To achieve maximum nephroprotection, it is advisable to add a non-dihydropyridine AK as a 3rd drug. verapamil, diltiazem), since these drugs enhance the nephroprotective effect of RAS blockers.

The mutually reinforcing effect of ACE inhibitors and verapamil was taken into account when creating the combination drug Tarka, consisting of trandolapril (hopten) 2 mg and verapamil SR 180 mg. If the clinical picture of vascular complications is dominated by ischemic heart disease, then the combination with a cardioselective beta-blocker is most effective. It must be remembered that it is impossible to combine BBs and non-dihydropyridines, since both groups of drugs suppress the conduction system of the heart, reducing heart rate. For the prevention of stroke, the most effective combination of RAS blockers and AK blockers of the dihydropyridine group.

If a combination of 3 drugs does not lead to achieving the target blood pressure level, then a drug from the AB group, centrally acting drugs, is added. As a rule, patients with diabetes with severe chronic renal failure require combination therapy of 4 drugs.

Clinical studies have shown that the most effective and safe combinations are:
. diuretic and BB;
. diuretic and ACEI (or ARB);
. AA (dihydropyridine) and BB;
. AK and ACEI (or ARA);
. AK and diuretic;
. AB and BB.

Thiazide diuretic + BB

This combination has proven itself in many studies (ALLHAT, STOP, MRC) as optimal for patients with uncomplicated hypertension without target organ damage. For ease of use, a fixed combination of BB and thiazide is available: bisoprolol (2.5, 5, 10 mg) + thiazide (6.25 mg). Since this combination contains a highly selective BB and a low dose of thiazide, it does not raise concerns regarding the risk of diabetes and can also be effectively used in patients with manifestations of the metabolic syndrome. The advantage of this combination is the fact that BB prevents the activation of the RAS caused by the diuretic.

Thiazide diuretic + ACE inhibitor

This combination is effective in patients with hypertension and congestive heart failure, isolated systolic hypertension, as well as in the elderly. This combination gives a fairly pronounced antihypertensive effect, so it is prescribed carefully to avoid a rapid decrease in blood pressure. There are drugs with fixed contents of ACE inhibitors and thiazide. For example, captopril (25, 50 mg) + thiazide (12.5 mg), enalapril (10, 20 mg) + thiazide (12.5 mg), fosinopril (10 mg) + thiazide (12.5 mg), benazepril ( 10 mg) + thiazide (12.5 mg), lisinopril (10.20 mg) + thiazide (12.5 mg). A highly effective combination of the ACE inhibitor perindopril with the thiazide-like diuretic indapamide is used, called “Noliprel” (perindopril 2.4 mg + indapamide 0.625 mg), as well as “Noliprel forte” (perindopril 2.4 mg + indapamide 1.25 mg).

In 2001, a multicenter randomized controlled trial ADVADCE (Action in Diabetes and VAscular Disease: Controlled Evaluation) was launched in 20 European countries (including Russia), the purpose of which was to determine the effectiveness of more intensive glycemic control and more intensive blood pressure control in patients with type 2 diabetes. with a high risk of developing vascular complications. The antihypertensive strategy in this study is prescribed regardless of the initial blood pressure level (even in normotensive patients) and is based on the addition of Noliprel to standard hypertension therapy.

The duration of the study is 4.5 years (results are expected after 2006). The study will answer still unresolved questions: is it possible to achieve not only secondary, but also primary prevention of vascular complications in the most severe category of patients - patients with type 2 diabetes.

The advantage of combining an ACEI and a diuretic is that the ACEI prevents RAS activation caused by the diuretic, and the diuretic promotes potassium excretion, thereby preventing hyperkalemia caused by the ACEI.

Thiazide diuretic + ARA

This combination may also be effective in hypertension and congestive heart failure, isolated systolic hypertension, as well as in LVH, since drugs from the ARA group are the most powerful agents that reduce hypertrophy. Fixed drug combinations include: losartan (50, 100 mg) + thiazide (12.5, 25 mg), valsartan (80, 160 mg) + thiazide (12.5 mg), irbesartan (150, 300 mg) + thiazide ( 12.5 mg). The advantages of this combination are the same as the combination of an ACE inhibitor and a thiazide diuretic.

Diuretic + AA (dihydropyridine)

Both diuretics and AA are effective in controlling blood pressure in isolated systolic hypertension in the elderly, so it is believed that this combination can be successfully used in the treatment of the above condition. An additional benefit of the combination is the elimination of leg swelling caused by AK.

Diuretic + I1-IR agonist

This combination has not yet been tested in large randomized trials. However, it can be assumed that it will be effective in individuals with IR syndrome, since imidazolines increase the sensitivity of peripheral tissues to insulin, as well as in patients with contraindications to the use of BB.

BB + AB

The indication for the use of this combination of drugs is hypertension against the background of hyperactivity of the sympathoadrenol system, accompanied by severe tachycardia and other manifestations of sympathocotony.

BB + ACEI

The antihypertensive activity of this combination is weaker than the combination of ACE inhibitors and diuretics. At the same time, the combined prescription of ACE inhibitors and beta-blockers is justified in the post-infarction period, in patients with coronary artery disease or congestive heart failure, since clinical studies have proven the effectiveness of both classes of drugs in these pathologies.

BB + AA (dihydropyridines)

This combination is prescribed to patients with hypertension and coronary artery disease. Both classes of drugs have an anti-ischemic effect, and their combined use leads to a mutually reinforcing effect. An additional advantage of this combination is the elimination of tachycardia caused by dihydropyridines.

ACEI + AA (dihydropyridines)

Over the past decade, this combination has been the most frequently prescribed. Both groups of drugs reduce blood pressure by acting on different mechanisms, and therefore complement each other. The rationale for combining ACEIs and ACs is presented below.

Dedov I.I., Shestakova M.V.

Catad_tema Complications of diabetes - articles

Catad_tema Arterial hypertension - articles

Pathogenesis of arterial hypertension in diabetes mellitus and side effects of used antihypertensive drugs

Literature review Mravyan S.P., Kalinin A.P.
MONIKA them. M.F. Vladimirsky

Due to the aging population of economically developed countries, there is a significant increase in both the cases of arterial hypertension (AH) and non-insulin-dependent diabetes mellitus (NIDDM). According to a number of researchers, 35-75% of diabetes complications from the cardiovascular system or kidneys can be associated with hypertension. Hypertension is observed in people with diabetes mellitus 2 times more often than in other groups of people. Lifestyle and heredity play an important role in the development of both diseases. Hypertension also contributes to the development of diabetic retinopathy, the leading cause of blindness in the United States. Based on these considerations, hypertension and diabetes mellitus should be diagnosed and actively treated as early as possible.

The majority of patients with NIDDM, who make up about 90% of people with diabetes mellitus and hypertension, have essential hypertension. Diabetic nephropathy occurs in a third of patients with insulin-dependent diabetes mellitus (IDDM) and in 20% of patients with NIDDM, being an important pathogenetic factor in the development of hypertension. Hypertension combined with diabetic nephropathy is characterized by fluid and sodium retention and an increase in total peripheral resistance. Patients with diabetes mellitus are characterized by the development of systolic hypertension, and the addition of autonomic neuropathy causes the rare occurrence of orthostic hypotension in them.

The mechanisms of the pathogenesis of vascular disorders in patients with diabetes mellitus and hypertension can be presented as follows:
1. Increased platelet adhesion and aggregation;
2. Anomalies of the coagulation system;
3. Pathology of lipoproteins;
4. Endothelial dysfunction;
5. Insulin-like growth factor-1 and vascular contractility;
6. The effect of hyperglycemia on vascular abnormalities in diabetes mellitus and hypertension.

In patients with diabetes mellitus, hemodynamic disturbances in the vessels of the kidneys and systemic circulation are largely similar. The similarity of functional and morphological changes in the microcirculation of the retina and glomeruli of the kidneys is shown. The appearance of albuminuria in patients with diabetes mellitus indicates not only the development of nephropathy, but also proliferative retinopathy. Similar to changes in the glomerular apparatus, microcirculatory changes in the retina occur several years before the development of retinopathy. Retinal hyperperfusion with dilatation of its arteries and veins was found in patients with the first signs of IDDM, at a stage when retinopathy is either not detected or is minimally expressed. Similar hyperperfusion is observed in the capillaries of the skin and subcutaneous fat of the forearm in patients with diabetes mellitus. The theory of glomerular hyperfiltration is supported by reports of increased plasma flow in the kidneys of most patients with IDDM without albuminuria. Increased filtration in the kidneys occurs acutely after the development of IDDM and is mediated by the following factors: hyperglycemia, hyperinsulinemia, increased levels of a number of hormones (growth hormone, glucagon, natriuretic peptide, insulin-like growth factor-1), ketone bodies and DR.

Disorders of autoregulation of peripheral capillary blood flow correspond to microcirculatory damage to the glomerular apparatus. Transcapillary release of albumin (TCA) indirectly reflects the transition of albumin from blood plasma to the kidneys and other tissues and is considered as a marker of damage to microcirculatory vessels. No changes in TVA were detected in patients with long-term IDDM and without signs of disease complications. At the same time, an increase in TVA was detected in patients with developed nephropathy and in patients without hypertension, but with microalbuminuria. The level of TVA is influenced by various factors. Thus, significant fluctuations in glycemia in a short time contribute to an increase in vascular permeability in patients with diabetes. The presence of hypertension in essential hypertension causes an increase in TVA, and there is a direct correlation between these indicators. However, moderate hypertension in IDDM is not considered as the initiating moment in the passage of albumin through the capillary membrane. In these patients, an increase in TVA was noted only with increased proteinuria. In cases of significant hypertension (essential or diabetes mellitus), an increase in TVA to a greater extent reflects hemodynamic disturbances in the microvasculature than damage to the filtration capacity of the kidneys. Thus, it has been shown that the mechanisms of initiation and maintenance of hypertension in patients with IDDM and diabetic nephropathy are different from those in patients without albuminuria.

Based on these data, the theory of generalized hyperperfusion is considered as the basis for the pathogenesis of complications of diabetes mellitus in the form of microangiopathy of the retina, renal glomeruli and peripheral vascular bed. A long-term consequence of severe hyperglycemia is an increase in the volume of extracellular fluid, leading to a decrease in renin content and an increase in the content of natriuretic peptide in the blood plasma, which, together with altered levels of other vasoactive hormones, lead to the generalization of the observed vasodilation. Generalized vasodilation causes thickening of the basement membrane in all capillaries and an increase in capillary pressure in the kidneys and retina.

Platelet adhesion and aggregation are significantly increased in both patients with diabetes and hypertension. The mechanisms responsible for platelet aggregation in both diseases are quite interrelated. Apparently, intracellular metabolism of divalent cations plays a certain role in these diseases. In the early stages of platelet activation, intracellular calcium and magnesium ions are of great importance. Platelet aggregation is associated with an increase in the intracellular calcium content necessary to initiate this process. Increasing intracellular magnesium in vitro has an inhibitory effect on platelet aggregation. A significant number of studies performed in hypertension and diabetes mellitus have revealed an increase in calcium content and a decrease in magnesium concentration in platelets. Thus, an imbalance in the intracellular content of divalent cations may play a role in increasing platelet aggregation in patients with diabetes mellitus and hypertension.

Platelet abnormalities in patients with diabetes mellitus and hypertension can be presented as follows:
1. Increased platelet adhesiveness;
2. Increased platelet aggregation;
3. Reduced platelet lifetime;
4. Increased tendency to form blood clots in vitro;
5. Increased production of thromboxane and other vasoconstrictor prostanoids by platelets;
6. Reduced production of prostacyclin and other vasodilating prostanoids by platelets;
7. Disturbance of homeostasis of divalent cations in platelets;
8. Increased non-enzymatic glycolysis of platelet proteins, including glycoproteins IIB and IIIA.

In patients with diabetes mellitus, the relationship between the coagulation and anticoagulation systems is maintained by several mechanisms. Hypercoagulation and damage to the fibrinolytic system in combination with platelet hyperactivation in patients with diabetes mellitus lead to hypertension, glycemic and lipidemic disorders with manifestations of vascular damage. Thus, in patients with diabetes mellitus, especially with damage to endothelial cells, micro- and macrovascular disorders and with unsatisfactory hypoglycemic therapy, there is an increase in the activity of a number of components of the coagulation system, including von Willebrand factor produced by the endothelium. It has been shown that a high concentration of components of factor VIII leads to hyperglycemia, an increase in the rate of thrombin formation and the growth of occlusive vascular lesions in patients with diabetes mellitus.

Increased fibrinogen binding and platelet aggregation in diabetic patients in response to adenosine diphosphate or collagen is mediated through increased production of prostaglandin H2, thromboxane A2, or both. A number of authors have shown that an increase in thromboxane production may be more likely due to high blood concentrations of glucose and lipids (or both) than to an increase in the interaction of platelets and the wall of blood vessels. However, the validity of these in vitro studies was later questioned by in vivo work. When determining the urinary excretion of most enzymatic metabolites of thromboxane B, it was not possible to identify statistically significant differences in diabetic patients with or without retinopathy and in the control group.

Lipoprotein disorders and pathology of the coagulation system, causing insulin resistance and hypertension in NIDDM, can be presented as follows:
1. Increased plasma levels of very low density lipoproteins (VLDL), low density lipoproteins (LDL) and lipoprotein (a);
2. Reducing the content of high-density lipoprotein (HDL);
3. Increase in triglyceride content in blood plasma;
4. Increased lipoprotein oxidation;
5. Increased glycolysis of lipoproteins;
6. Increase in the content of LDL products;
7. Decreased lipoprotein lipase activity;
8. Increase in fibrinogen and plasminogen activator inhibitor-1;
9. Decrease in the content of plasminogen activator and fibrinolytic activity;
10 Decreased angiotensin III levels, protein C and S levels.

In diabetes mellitus and hypertension, a number of anatomical and functional disorders of the vascular endothelium develop:
1. Increase in the content of von Willebrand factor in the blood plasma;
2. Increased expression, synthesis and content of endothelin-1 in the blood plasma;
3. Limitation of prostacyclin production;
4. Decreased production of endothelium-dependent relaxation factor (NO) and decreased sensitivity to it;
5. Damage to fibrinolytic activity;
6. Impaired degradation of plasmin by glycolyzed fibrin;
7. Increase in endothelial cell surface of thrombomodelin;
8. Increased endothelial cell procoagulant activity;
9. Increased levels of glycosylation end products.

The presence of hyperglycemia is possibly dependent on endothelial function. Isolated vascular segments obtained from animals with diabetes mellitus showed impaired endothelium-dependent relaxation, which could also be caused by incubation of normal vessels at high glucose concentrations. Hyperglycemia activates protein kinase C in endothelial cells, which can cause an increase in the production of vasoconstrictor prostaglandins, endothelin and angiotensin-converting enzyme, which have a direct or indirect damaging effect on vasomotor reactivity. Moreover, hyperglycemia impairs matrix production by endothelial cells, which can lead to increased basement membrane thickness. Hyperglycemia increases the synthesis of type IV collagen and fibronectin by endothelial cells with an increase in the activity of enzymes involved in collagen synthesis. Hyperglycemia also delays replication and causes the growth of dead endothelial cells, possibly due to increased oxidation and glycolysis.

A number of metabolic and hemodynamic factors can influence endothelial dysfunction in patients with diabetes and hypertension. Hypercholesterolemia, and possibly hypertriglyceridemia, impairs endothelium-dependent relaxation. Both insulin and insulin-like growth factor (IGF) can act on endothelial cells by stimulating DNA synthesis. There is a hypothesis that endothelial dysfunction in diabetes is associated with an increase in protein kinase C activity in the vascular endothelium, which leads to increased vascular tone and the development of atherosclerosis.

IGF-1 is expressed, synthesized and released by smooth muscle cells. IGF-1, like insulin, increases K-Na-ATPase activity of smooth muscle cells and reduces vascular contractility.

Constant hyperglycemia increases vascular diseases associated with diabetes mellitus and hypertension. At high concentrations, glucose has a direct (osmolarity-independent) toxic effect on vascular endothelial cells. This toxic effect may lead to decreased endothelium-dependent vascular relaxation, increased vasoconstriction, stimulation of smooth muscle cell hyperplasia, vascular remodeling, and the development of atherosclerosis.

Hyperglycemia also increases the formation of glycosylation products, which accumulate in the vascular wall. Non-enzymatic glycosylation of proteins goes through three stages, which in vivo depend on the degree and duration of hyperglycemia, protein half-life and tissue permeability to free glucose. Through a number of mechanisms, non-enzymatic glycosylation proteins are able to influence key processes of atherogenesis and vascular remodeling. A relationship has been shown between the accumulation of end products of protein glycosylation and vascular diseases. Thus, ongoing hyperglycemia leads to increased extracellular matrix production and smooth muscle cell proliferation with vascular hypertrophy and remodeling. Hyperglycemia is associated with a decrease in the elasticity of the connective tissue of the arteriolar walls and an increase in pulse pressure. In addition, hyperglycemia leads to increased filtration of glucose, which stimulates the sodium-glucose transporter in the proximal tubule. Sodium retention caused by hyperglycemia may explain the overall increase in sodium in diabetic patients. Impaired sodium excretion in IDDM is influenced by a number of pathogenetic factors associated with increased sodium reabsorption in the renal tubules. Sodium reabsorption is enhanced in the presence of glucose and ketone bodies. An antisodium-uretic effect has been noted when using insulin in vivo, and insulin only promotes sodium reabsorption in the proximal or distal tubules of the kidneys.

All authors consider the relationship between diabetes mellitus and hypertension with an emphasis on kidney damage. Diabetic nephropathy is the leading cause of late-stage kidney disease in the United States. Hypertension is a significant risk factor for the progression of kidney damage in diabetes mellitus. Finally, assessing the relationship between diabetes mellitus, hypertension and diabetic nephropathy can play a significant role in the selection of rational drug therapy.

Morbidity and mortality, both in patients with NIDDM and IDDM, are largely determined by the development of diabetic nephropathy. For example, in patients with IDDM with transient proteinuria, mortality is 37-80 times higher than in the general population of healthy people.

The pathogenesis of diabetic nephropathy has been studied previously. Patients with a genetic predisposition to diabetes mellitus, hypertension, or both diseases are more vulnerable to vascular damage when significant hyperglycemia develops than patients with the same degree of hyperglycemia but without a genetic predisposition.

The subclinical stage of nephropathy, characterized by microalbuminuria, is either preceded by hypertension, or its development occurs along with an increase in blood pressure. The use of 24-hour blood pressure monitoring in patients with IDDM with microalbuminuria without hypertension revealed a physiological nocturnal decrease in blood pressure. This circumstance is closely related to the development of autonomic neuropathy, which can influence the development of diabetic nephropathy through changes in the daily blood pressure profile.

The pathogenesis of the influence of hyperinsulinemia and insulin resistance on the development of hypertension is not completely clear. However, it has been found that hyperinsulinemia can lead to hypertension through the effects of vascular remodeling and atherosclerotic changes.

Thus, with IDDM in the absence of diabetic nephropathy, blood pressure most often remains normal, but soon increases (within 1-2 years) after the appearance of signs of the initial stage of nephropathy - microalbuminuria from 30 to 300 mg / day - and rapidly progresses as clinical signs appear nephropathy and renal failure. This indicates that the renal parenchymal mechanism(s) underlies hypertension.

In contrast, in NIDDM, hypertension can develop before the onset of symptoms of diabetic nephropathy and in 50% of cases is already present in patients when NIDDM is diagnosed, as well as some other metabolic disorders, such as obesity and dyslipidemia. This gives reason to believe that such patients, before the onset of diabetes mellitus, must already have certain hormonal and metabolic disorders as part of hypertension, and also that both of these diseases have a common pathophysiological basis.

Choosing an antihypertensive drug for diabetes mellitus

The choice of antihypertensive therapy in patients with diabetes is not simple, since this disease imposes a number of restrictions on the use of a particular drug, taking into account the range of its side effects and, above all, the effect on carbohydrate and lipid metabolism. When choosing the optimal antihypertensive drug for diabetes mellitus, it is necessary to take into account associated vascular complications.

Diuretics

The use of drugs of this group in patients with diabetes mellitus is quite justified, given the observed sodium and fluid retention in patients with both IDDM and NIDDM.

However, high-dose thiazide diuretics (50 mg hydrochlorothiazide or equivalent doses of other diuretics) increase fasting glucose levels and glycosylated hemoglobin concentrations and impair tolerance to oral and intravenous glucose loads. Proposed mechanisms of impaired glucose tolerance during treatment with thiazide diuretics include a decrease in insulin secretion and a decrease in tissue sensitivity to the action of insulin (insulin resistance).

In addition, the use of thiazide diuretics can increase the risk of diabetes mellitus in elderly and senile people. Thiazide diuretics increase the risk of developing type 2 diabetes independently of other risk factors, according to a 10-year study. Finally, according to a retrospective study, thiazide diuretics accelerate the development of diabetic nephropathy in diabetic patients with hypertension.

Thus, in the treatment of arterial hypertension in patients with diabetes mellitus, only loop diuretics and thiazide-like drugs can be successfully used. The former do not have a diabetogenic effect, do not disrupt lipid metabolism and have a beneficial effect on renal hemodynamics. The latter do not affect carbohydrate and lipid metabolism and do not impair the filtration function of the kidneys, which makes their use safe in patients with chronic renal failure.

b-blockers

Like thiazide diuretics, b-blockers have a range of undesirable metabolic effects: they impair carbohydrate tolerance, increase insulin resistance, and have a hyperlipidemic effect. Basically, all metabolic effects of b-blockers are associated with blockade of b2-adrenergic receptors. Interestingly, b-blockers with intrinsic sympathomimetic activity have little effect on carbohydrate metabolism.

The creation of selective b-blockers has largely made it possible to overcome the undesirable metabolic effects of this group of drugs. However, it is important to remember that as the dose of a cardioselective b-blocker is increased, the cardioselective effect is “lost.” It is not recommended to prescribe b-blockers to patients with IDDM with frequent hypo- and hyperglycemia, as well as to patients with impaired recognition of hypoglycemic conditions (due to the development of autonomic neuropathy). Subjective sensations of developing hypoglycemia are associated with activation of adrenergic receptors. Blockade of the latter can lead to the development of coma without subjective warning signs.

a-blockers

These drugs do not disrupt lipid metabolism, but reduce the atherogenicity of blood serum, reducing the level of LDL and triglycerides. A significant side effect of a-blockers is the development of postural hypotension. It often complicates the course of diabetes due to the development of autonomic polyneuropathy.

Centrally acting drugs

Centrally acting drugs have a number of side effects that can be very undesirable in patients with diabetes (drowsiness, sedation, dry mouth, severe withdrawal syndrome and provocation of hypertension crises).

A new group of drugs in this series - 12-imidazoline receptor antagonists (moxonidine) - are devoid of these side effects and have proven themselves best in patients with diabetes mellitus.

Calcium antagonists

Drugs in this group do not affect carbohydrate and lipid metabolism, so they can be used safely and with great effectiveness in patients with diabetes mellitus and hypertension.

ACE inhibitors

In recent years, these drugs have become most popular due to their high hypotensive activity and few side effects. Like calcium antagonists, they are metabolically neutral, eliminate insulin resistance and are able to restore the early peak of insulin secretion. ACE inhibitors have a powerful organoprotective effect, which is of particular importance in patients with diabetes mellitus suffering from damage to the heart, kidneys, and retinal vessels. In addition, drugs in this group have an antiproliferative effect on smooth muscle cells of arterioles.

The only contraindication for the use of ACE inhibitors in patients with diabetes is bilateral renal artery stenosis. This complication must be kept in mind in patients with generalized atherosclerosis.

Thus, in patients with diabetic nephropathy, ACE inhibitors, as well as verapamil and diltiazem, can be considered first-line antihypertensive drugs. If monotherapy with ACE inhibitors is insufficiently effective, a calcium antagonist or diuretic (primarily indapamide) should be added. The presented data indicate that approaches to the treatment of hypertension in patients with diabetes mellitus differ significantly from approaches to the treatment of uncomplicated hypertension. The latter statement is largely based on the practitioner's knowledge of the side effects of a wide range of antihypertensive drugs used.

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For quotation: Preobrazhensky D.V., Sidorenko B.A. Arterial hypertension in diabetes mellitus // RMJ. 1999. No. 7. P. 13

Arterial hypertension occurs in patients with diabetes mellitus approximately 2 times more often than in the general population. The incidence of arterial hypertension among patients with diabetes mellitus ranges from 20 to 60%, depending on the criteria used for high blood pressure (BP) and the type of diabetes mellitus. Arterial hypertension has a significant impact on the fate of patients with diabetes, significantly increasing the risk of developing cardiovascular and renal complications, which are the main causes of their premature death. Thus, according to the Framingham study, arterial hypertension increases mortality among patients with diabetes by 5 times. In patients with diabetes mellitus and arterial hypertension, effective drug therapy significantly prevents the development of cardiovascular complications and renal failure. Antihypertensive drugs are recommended for all adult patients with diabetes mellitus with a blood pressure level of 130/85 mmHg. Art. and more.

Forms of arterial hypertension in patients with diabetes mellitus

In patients with diabetes mellitus, two forms of arterial hypertension are most common: 1) hypertension and 2) hypertension associated with diabetic nephropathy. In addition, the causes of arterial hypertension in patients with diabetes may be stenotic lesions of the renal arteries (unilateral and bilateral), diffuse glomerulonephritis, chronic pyelonephritis, necrosis of the renal papillae.
Hypertension is the predominant form of arterial hypertension in patients with insulin-independent diabetes mellitus (type II). Approximately In 10 - 20% of patients with type II diabetes mellitus, the cause of arterial hypertension is diabetic nephropathy. In some cases, arterial hypertension may be associated with stenotic lesions of one or both renal arteries.
Table 1. Effects of various antihypertensive drugs on glucose metabolism.

Preparation	Glucose level	Insulin secretion	Tissue sensitivity to insulin
Thiazide diuretics
Indapamide
b -Adrenergic blockers:
Non-selective
b 1 -selective	0/ -	0/ Ї	Ї /0
Calcium antagonists
ACE inhibitors	0/ Ї		0/ -
AT 1 receptor blockers
a 1 -Adrenergic blockers	0/ Ї		0/ -
Agonists a 2 -adrenoreceptors		0/s
I 1 receptor agonists

In the vast majority of patients with insulin-dependent diabetes mellitus (type I), in the first years after the onset of the disease, blood pressure is within the age-related norm. Approximately 10 to 15 years after the onset of the disease, 50% of patients with type 1 diabetes develop diabetic nephropathy, which is characterized by persistent proteinuria, arterial hypertension and progressive renal dysfunction (decreased glomerular filtration rate below 80 ml/min, increased serum creatinine levels). At the preclinical stage, diabetic nephropathy is manifested by an increased glomerular filtration rate (more than 130 - 140 ml/min) and microalbuminuria (30 - 300 mg/day or 20 - 200 mcg/min). Blood pressure can be either normal or elevated, but average blood pressure levels in patients with latent diabetic nephropathy are significantly higher than in healthy individuals of the same age.

Table 2. Effect of nisoldipine and enalapril on mortality and cardiovascular complications in patients with type II diabetes mellitus and arterial hypertension

Exodus	Nisoldipine (n = 235)	Enalapril (n = 235)	Relative risk	Relative risk as amendedto other factors
			5,5 (2,1 - 14,6)	7,0 (2,3 - 21,4)
Nonfatal cases of myocardial infarction			4,8 (1,8 - 12,8)	5,9 (1,9 - 18,2)
Cerebrovascular accident			1,6 (0,6 - 4,2)	2,2 (0,7 - 7,1)
Congestive heart failure			1,2 (0,4 - 4,0)	1,3 (0,3 - 5,9)
Death from cardiovascular causes			2,0 (0,7 - 6,1)	1,4 (0,4 - 5,1)
Death from any cause			1,3 (0,6 - 2,8)	1,0 (0,4 - 2,3)

Choosing an antihypertensive drug for the treatment of arterial hypertension in a patient with diabetes mellitus

As mentioned, antihypertensive drugs must be prescribed to all patients with diabetes mellitus with a blood pressure level of at least 130/85 mmHg. Art. based on repeated measurements. When choosing a drug for long-term treatment of arterial hypertension in patients with diabetes, one should take into account not only the severity of its antihypertensive effect, but also the possible effect on carbohydrate metabolism and the pathogenetic mechanisms of arterial hypertension.
Currently, the following groups of antihypertensive drugs are used to treat hypertension: thiazide diuretics, b -adrenergic blockers, calcium antagonists, angiotensin-converting enzyme (ACE) inhibitors, AT1-angiotensin receptor blockers, blockers a 1 -adrenergic receptors, central a 2 -adrenergic receptor agonists and I1-imidazoline receptor agonists.

Table 3. The effect of fosinopril and amlodipine on mortality and the incidence of cardiovascular complications in patients with hypertension in combination with type II diabetes mellitus (per 100 patients per year)

Event	Fosinopril (n =189)	Amlodipine (n = 191)	Relative risk
Death from any cause	0,7 (4)	0,9 (5)
Fatal and non-fatal stroke cases	0,7 (4)	1,9 (10)	0,39 (0,12 - 1,23)
Fatal and non-fatal cases of myocardial infarction	1,8 (10)	2,4 (13)	0,77 (0,34 - 1,75)
Angina pectoris requiring hospitalization of the patient	0 (0)	0,7 (4)
Any serious cardiovascular complication	2,6 (14)	5,0 (27)	0,49 (0,26 - 0,95)
The number of events is indicated in brackets

Table 4. The effect of various antihypertensive drugs on the severity of micro- and macroalbuminuria in patients with diabetes mellitus (summary literature data)

Antihypertensive drugs	Number of patients	Changes, %
		Average blood pressure	Protein excretion in urine
Diuretics or b - adrenergic blockers			23 (-11/-35)
ACE inhibitors	1061		45 (-25/-64)
Calcium antagonists:
Generally			17 (-2/-33)
Nifedipine			5(+31/-21)
All others except nifedipine			35 (-24/-47)
Verapamil/diltiazem			41 (-23/-49)
ACE inhibitor + verapamil
*r< 0,05 по сравнению с монотерапией

The effect of antihypertensive drugs on carbohydrate metabolism

In individually selected doses, drugs belonging to different pharmacological groups have the same effect on blood pressure, but they differ in their effect on carbohydrate metabolism, urinary albumin excretion and renal function.
Antihypertensive drugs can be divided into three main groups depending on their effect on carbohydrate metabolism:
1. Drugs that have an adverse effect on carbohydrate metabolism (diuretics, with the exception of indapamide, and beta-blockers).
2. Drugs that do not have a significant effect on carbohydrate metabolism (indapamide, b-adrenergic blockers with vasodilating properties, calcium antagonists, AT1-angiotensin receptor blockers, central a2-adrenergic receptor agonists).
3. Drugs that have some beneficial effect on carbohydrate metabolism (ACE inhibitors, a 1 -blockers and I 1 agonists -imidazoline receptors).
Thiazide diuretics andβ-blockers, usually recommended for use in patients with uncomplicated hypertension, are not entirely suitable for the treatment of arterial hypertension in patients with diabetes mellitus. First, thiazide diuretics and beta-blockers can impair glucose tolerance. Secondly, according to some observations, they predispose to the onset and, possibly, progression of diabetes mellitus in patients with hypertension.
High-dose thiazide diuretics (50 mg hydrochlorothiazide or equivalent doses of other diuretics) increase fasting glucose levels and concentration of glycosylated hemoglobin, and also impair tolerance to oral and intravenous glucose load. Cases of the development of non-ketonemic hypersmolar coma during treatment with thiazide diuretics in patients with diabetes mellitus have been described. Proposed mechanisms of impaired glucose tolerance during treatment with thiazide diuretics include a decrease in insulin secretion and a decrease in tissue sensitivity to the action of insulin (insulin resistance) ().
b -Adrenergic blockers impair glucose tolerance. In patients with diabetes mellitus, they aggravate hyperglycemia and in some cases can cause the development of non-ketonemic hypersmolar coma. Non-selective drugs have the most adverse effect on glucose metabolism. b -adrenergic blockers (propranolol, nadolol, timolol) and b 1-selective blockers (atenolol, metoprolol, etc.) in high doses. On the other hand, b -adrenergic blockers with internal sympathomimetic activity (oxprenolol, pindolol, etc.) have a slight effect on carbohydrate metabolism.
Proposed mechanisms of impaired glucose tolerance during treatment b -adrenergic blockers include inhibition of insulin secretion, decreased tissue sensitivity to the action of insulin (insulin resistance), inhibition of glucose utilization in peripheral tissues and increased secretion of growth hormone.
Along with impaired glucose tolerance, the ability to b -adrenergic blockers mask the clinical manifestations of hypoglycemia and inhibit the mobilization of glucose from the liver in response to hypoglycemia. As is known, many symptoms and signs of hypoglycemia are caused by increased activity of the sympathetic-adrenal system. All b-adrenergic blockers, suppressing the clinical manifestations of hypersympathicotonia, can complicate the diagnosis of hypoglycemic conditions in patients with diabetes mellitus.
b -Adrenergic blockers inhibit the mobilization of glucose from the liver in response to hypoglycemia, both spontaneous (for example, after intense exercise or prolonged fasting) and induced by insulin or oral hypoglycemic drugs. Glucose mobilization from the liver is mediated b 2 -adrenergic receptors. Therefore, hypoglycemic reactions to insulin and oral hypoglycemic drugs are more often observed during treatment with non-selective b - adrenergic blockers.
Thus, in diabetes mellitus b -adrenergic blockers (especially non-selective ones), on the one hand, impair glucose tolerance, and on the other hand, predispose to the development of hypoglycemia and complicate the timely diagnosis of hypoglycemic conditions.
Several population studies have shown that thiazide diuretics andβ-blockers increase the likelihood of developing diabetes mellitus in middle-aged and elderly hypertensive patients. Thus, C. Bengtsson et al. reported a 3.5-fold increase in the risk of diabetes mellitus in women with hypertension treated with thiazide diuretics compared with untreated patients. Thiazide diuretics increase the risk of developing type 2 diabetes independently of other risk factors, according to a 10-year study. In a comparative study, the incidence of diabetes mellitus was 2 to 3 times higher in elderly hypertensive patients receiving b -adrenergic blockers or thiazide diuretics, compared with untreated patients. Finally, according to a retrospective study, thiazide diuretics accelerate the development of diabetic nephropathy in diabetic patients with arterial hypertension.
Suggestion of adverse effects of thiazide diuretics and b -adrenergic blockers on the onset and progression of diabetes mellitus in patients with arterial hypertension, based on the results of retrospective and uncontrolled prospective studies, was recently confirmed in the CAPPP study (Captopril Prevention Project, 1998). In this controlled study, the incidence of diabetes mellitus over 6 years of follow-up was significantly higher in the group of hypertensive patients treated with diuretics and b -adrenergic blockers, compared with patients receiving the ACE inhibitor captopril.
Considering the effect of antihypertensive drugs on carbohydrate metabolism, in the treatment of arterial hypertension in patients with diabetes mellitus without concomitant damage to the heart and kidneys, ACE inhibitors and blockers should be used first. a 1 -adrenergic receptors and I1-imidazoline receptor agonists ( ).
However, the ability of antihypertensive drugs to prevent cardiovascular and renal complications in patients with diabetes is much more important than their effect on carbohydrate metabolism.

Effect of antihypertensive drugs on cardiovascular complicationsin patients with diabetes mellitus

Unfortunately, the preventive effectiveness of various antihypertensive drugs in patients with diabetes has not been sufficiently studied in long-term studies. Controlled studies have demonstrated the ability of thiazide diuretics and b -adrenergic blockers prevent cardiovascular complications in diabetic patients with arterial hypertension, despite the adverse effect on glucose metabolism. Recently published results of the CAPP study (1998) indicate that in patients with hypertension in combination with diabetes mellitus, the ACE inhibitor captopril is more effective in preventing cardiovascular complications than diuretics and b - adrenergic blockers. Two other controlled studies have shown the superiority of ACE inhibitors over “vasoselective” calcium antagonists in the prevention of cardiovascular complications in patients with hypertension in combination with type II diabetes mellitus. Thus, in the controlled ABCD (Appropriate Blood Pressure Control Diabetes) study, in patients with type II diabetes mellitus with arterial hypertension treated with the ACE inhibitor enalapril, myocardial infarction and other cardiovascular complications developed significantly less frequently than in the group of patients receiving the calcium antagonist nisoldipine ( ).
In the randomized trial FACET (Fosinopril versus Amlodipine Cardiovascular Events randomized Trial) cardiovascular complications developed significantly less frequently in the group of patients with hypertension in combination with type II diabetes mellitus treated with the ACE inhibitor fosinopril, compared with patients receiving the calcium antagonist amlodipine ( ).
Ability a 1 -adrenergic blockers and I1-imidazoline receptor agonists to improve long-term prognosis in diabetic patients with arterial hypertension, to our knowledge, have not been studied. Therefore, taking into account the results of the controlled studies KAPPP, ABCD and FACET, ACE inhibitors can be considered the drugs of choice for the treatment of hypertension in patients with type II diabetes mellitus.
If the antihypertensive effectiveness of ACE inhibitors is insufficient, calcium antagonists and/or diuretics are added. Recent studies have demonstrated the cardioprotective effects of a combination of an ACE inhibitor and dihydropyridine calcium antagonists such as amlodipine and felodipine retard.
b 1 -Selective b -blockers (atenolol, betaxolol, bisoprolol, metoprolol, etc.) still play an important role in the treatment of arterial hypertension in patients with diabetes mellitus in combination with coronary artery disease. After all, patients with coronary artery disease have a particularly high risk of sudden death and the development of myocardial infarction, which prevent b - adrenergic blockers.

Effect of antihypertensive drugs on proteinuria and renal functionin patients with diabetes mellitus

Antihypertensive drugs have different effects on urinary albumin excretion, which reflects the severity of kidney damage and is an unfavorable prognostic sign in type I diabetes mellitus ( ).
ACE inhibitors and “cardioselective” calcium antagonists (verapamil and diltiazem) when prescribed as monotherapy to the greatest extent reduce micro- and macroalbuminuria in patients with diabetes (on average by 20 - 60%). When combined with verapamil or diltiazem, ACE inhibitors reduce urinary albumin excretion by almost 80%. Of the diuretics, indapamide is comparable to ACE inhibitors in its effect on urinary albumin excretion in patients with diabetic nephropathy.
Numerous controlled studies have established the ability of ACE inhibitors to slow the progression of diabetic nephropathy in patients with type I diabetes mellitus. Thus, E. Lewis et al. showed that long-term therapy with captopril reduces the risk of renal complications by approximately 50% in diabetic patients with overt nephropathy. Captopril was equally effective in patients with high and normal blood pressure.
Other studies have found a beneficial effect of inhibitors on the progression of latent diabetic nephropathy (urinary albumin excretion rate from 30 to 300 mg/day) in patients with type I diabetes mellitus. According to summary data from three long-term studies, treatment with ACE inhibitors more than 4 times reduces the likelihood of transformation of latent diabetic nephropathy into overt (urinary albumin excretion rate more than 300 mg/day).
The evidence for the renoprotective effect of ACE inhibitors in patients with type II diabetes mellitus with overt nephropathy is not so convincing. For example, M. Ravid et al. found that the ACE inhibitor enalapril, when used long-term, prevents the development of renal dysfunction in patients with type II diabetes mellitus with microalbuminuria.
In short-term comparative studies, “cardioselective” calcium antagonists had the same beneficial effects on urinary albumin excretion rate and renal function in patients with overt diabetic nephropathy as ACE inhibitors. Results from studies examining the renal effects of long-acting “vasoselective” antagonists are conflicting.
Thus, in patients with diabetic nephropathy, ACE inhibitors, as well as verapamil and diltiazem, can be considered first-line antihypertensive drugs. If monotherapy with an ACE inhibitor is insufficiently effective, a calcium antagonist (verapamil or diltiazem) or a diuretic (primarily indapamide) should be added.

Goals of antihypertensive therapy in patients with diabetes mellitus

Until recently, it was recommended to maintain blood pressure in patients with diabetes at a level no higher than 130/85 mm Hg. Art. The controlled HOT (Hypertension Optimal Treatment) study showed that in patients with diabetes mellitus it is advisable to reduce blood pressure to a lower level. In this study, mortality and incidence of cardiovascular events were lowest in the group of patients whose diastolic blood pressure was maintained at 80 mmHg. Art. and below.
In MDRD studies (Modifica tion of Diet in Renal Disease) shows that in patients with kidney damage of various etiologies, the desired level of blood pressure reduction depends on the severity of proteinuria. In patients with proteinuria more than 1 g/day, the optimal blood pressure level in terms of progression of renal dysfunction is 125/75 mm Hg. Art. and lower, and in patients with daily proteinuria from 0.25 to 1.0 g - 130/80 mm Hg. Art. In patients with proteinuria less than 0.25 g/day, it is enough to maintain blood pressure at a level not higher than 130/85 mm Hg. Art. .
Therefore, in most cases, patients with diabetes should maintain blood pressure at a level not higher than 130/80 mmHg. Art. And only in patients with diabetic nephropathy and severe proteinuria is it important to reduce blood pressure to a lower level.
Thus, the presented literature data indicate that approaches to the treatment of arterial hypertension in patients with diabetes mellitus differ significantly from approaches to the treatment of uncomplicated hypertension. Non-thiazide diuretics andβ-blockers should be primarily used for the treatment of arterial hypertension in patients with diabetes mellitus, and ACE inhibitors, the preventive effectiveness of which in diabetes mellitus has been proven in three controlled studies. In patients with diabetes mellitus, drug antihypertensive therapy should be started at lower blood pressure levels, which are not formally considered elevated. The level of blood pressure, which must be maintained with the help of antihypertensive drugs, is also lower in patients with diabetes mellitus than in hypertensive patients without diabetes mellitus.

Literature:

1. Wilson PW, Cupples CF, Kannel WB. Is hyperglycemia associated with cardiovascular disease? The Framingham Study. - Amer. Heart J 1991;121:586-90.
2. The sixth report of the Joint National Committee on prevention, detection, evaluation abd treatment of high blood pressure - Arch. Intern. Med 1997;157(11):2413-46.
3. Houston MC. The effects of antihypertensive drugs on glucose intolerance in hypertensive nondiabetic and diabetics -Amer Heart J 1988;115(3):640-56.
4. Bengtsson C, Blohme G, Lapidus L, Lundgren H. Diabetes in hypertensive women: an effect of antihypertensive drugs or the hypertensive state per se? - Diabetes Med. 1988;5:261-4.
5. Skarfors ET, Selinus KI, Lithell HO. Risk factors for the development of noninsulin-dependent diabetes in middle-aged men - Brit. Med. J 1991;303:755-60.
6. Mykkanen L, Kuusisto J, Pyorala K. et al. Increased risk of non-insulin-dependent diabetes mellitus in elderly hypertensive subjects - J. Hypertens 1994;12:1425-32.
7. Walker WG, Herman J, Yin DP. et al. Diuretics accelerated diabetic nephropathy in hypertensive insulin-dependent and non-insulin-dependent subjects - Trans. Amer. Assoc. Phys. 1987;100:305-15.
8. Estacio RO, Jeffers BW, Hatt WR. et al. The effect of nisoldipine as compared with enalapril on cardiovascular outcomes in patients with enalapril on cardiovascular outcomes in patients with non-insulin-dependent diabetes and hypertension - New Engl. J. Med. 1998;338(10):645-52.
9. Tatti P, Guarisco R, Pahor M. et al. Outcome results of the fosinipril versus amlodipine cardiovascular events randomized trial (FACET) in patients with hypertension and NIDDM - Diabetes Care 1998;21 (4):597-603.
10. Lewis EJ, Hunsicker LO, Baix R. et al. The effects of angiotensin-converting enzyme inhibition on diabetic nephropathy - New Engl. J Med 1993;329(20):1456-62.
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Antihypertensive drugs for type 2 diabetes mellitus are selected individually, taking into account their effect on kidney function and the effect on the metabolism of fatty acids and carbohydrates. Arterial hypertension accompanies 80% of those suffering from hyperglycemia. Diseases mutually aggravate the functioning of internal organs and disrupt natural metabolic processes.

Peculiarities

Prescribing blood pressure pills for diabetics is complicated by possible undesirable effects, the manifestation of which is caused by impaired intracellular metabolism.

The choice of drugs for hypertension in hyperglycemia is based on the following conditions:

• Maximum effectiveness, minimum side effects;
• Cardio- and nephroprotective effects (protection of the heart and kidneys);
• No effect on blood lipid and glucose concentrations.

Fast acting medications

If you are prone to sudden jumps in blood pressure, individually suitable medications for hypertension and diabetes should be on hand.

It is unacceptable to accidentally consume substances that can aggravate the development of insulin resistance in a diabetic.

If emergency relief is necessary, use drugs whose effect on the body lasts no more than 6 hours. Active substances included in common trade names of medicines:

Medicines for systematic use

Constant readings above 130/80 mmHg. Art. for diabetics, they are fraught with microvascular complications, the development of atherosclerosis, and the progression of diabetic angiopathy. In this case, constant use of medications is recommended, while simultaneously following a salt and carbohydrate diet. The effects of high blood pressure medications for diabetes should be gradual. A drop in blood pressure followed by a jump upward is destructive even for the cardiovascular system of a healthy person.

ACE inhibitors

To gradually stabilize the manifestations of hypertension, angiotensin-converting enzyme (ACE) blockers are used, which stimulates the synthesis of angiotensin. By reducing the concentration of angiotensin, the adrenal glands produce less of the hormone aldosterone, which retains sodium and water in the body. Vasodilation occurs, excess fluids and salts are removed, and a hypotonic effect appears.

Active substances that block ACE:

• Enalapril;
• Perindopril;
• Quinapril;
• Fosinopril;
• Trandolapril;
• Ramipril.

They are characterized by a nephroprotective effect (slow down pathological processes), do not disrupt the metabolism of carbohydrates, lipids, or insulin resistance of tissues.

The disadvantages of inhibitors are the ability to delay potassium excretion and delayed effectiveness. The consequences of use are assessed no earlier than two weeks after prescription.

Angiotensin receptor blockers (ARBs)

They block the synthesis of renin, which stimulates the transformation of angiotensin, which causes a narrowing of the vascular walls. ARBs are prescribed if intolerance to ACE inhibitors is established. The mechanism of their biochemical tactics is different, but the goal is the same - reducing the effects of angiotensin and aldosterone.

The group is called sartans after the endings of the names of the active substances:

• Irbesartan;

Diuretics

Diuretics have a mild hypotonic effect and are prescribed mainly in complex therapy with the use of other tablets for hypertension in diabetes mellitus.

1. Loop diuretics (furosemide, lasex) combine well with ACE inhibitors, do not affect sugar or lipid levels, and are suitable for short-term use to eliminate severe tissue swelling. Uncontrolled use provokes accelerated excretion of potassium, which can provoke increased hypokalemia and cardiac arrhythmia.
2. Thiazide-like diuretics (indapamide), due to their mild diuretic effect, do not disturb the balance of glucose, fatty acids, potassium levels, and do not affect the natural functioning of the kidneys.
3. Thiazide diuretics (hypothiazide) in daily doses exceeding 50 mg can increase glucose and cholesterol levels. Prescribed with caution in minimal doses due to the likelihood of worsening renal failure and gout.
4. Potassium-sparing substances (veroshpiron) are not recommended for use in type 2 diabetes mellitus, accompanied by impaired renal function.

A number of drugs that block the stimulation of adrenergic receptors by adrenaline and norepinephrine are prescribed primarily for the treatment of ischemia, cardiosclerosis, and heart failure. For hyperglycemia, tablets for hypertension are selected with an additional vasodilating effect:

• Labetalol;
• Carvedilol;
• Nebivolol.

The action of B-blockers can produce an effect that masks the manifestation of glycemia, so they are prescribed with caution, monitoring glucose concentrations.

Calcium antagonists

Calcium channel blockers are a group of drugs that reduce the concentration of calcium ions. They relax and expand the walls of blood vessels, arteries, and smooth muscle cells. Conditionally divided into groups.

The combination of diseases such as arterial hypertension and diabetes mellitus requires special attention from the patient and the doctor. Hypertension does not increase the likelihood of diabetes, but diabetes is a known risk factor for hypertension. It is accompanied by increased blood pressure in at least a third of patients. Hypertension significantly increases the risk of damage to the coronary and renal arteries in patients with diabetes, which worsens the prognosis of the disease. Therefore, timely detection and treatment of high blood pressure is important.

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Forms of the disease

Elevated glucose levels in diabetes damage the inner surface of the vascular bed. This disrupts the production of vasodilator substances in it, reduces the elasticity of the arteries and leads to the development of hypertension.

When the kidney vessels are damaged, which is typical for diabetes, diabetic nephropathy occurs. At the same time, the kidneys begin to secrete many vasoconstrictor substances that cause.

Key treatment goals

Hypertension and diabetes mellitus aggravate each other. The progression of the pathology is accompanied by an increased risk of complications (heart attack, stroke, heart failure) and renal failure.

Treatment of arterial hypertension in diabetes mellitus has the following main goals:

• reducing the risk of complications from the heart and blood vessels;
• reducing mortality from these complications;
• prevention of renal failure;
• improving the patient's quality of life;
• maintaining normal blood glucose levels (neutral effect on carbohydrate metabolism).

Therapy begins in a situation where a person with diabetes has a pressure level greater than or equal to 130/85 after several measurements. It is necessary to select a combination of medications to maintain blood pressure no more than 130/80. In the case of severe kidney damage, accompanied by a daily protein excretion of more than 1.0 g, a blood pressure value of no higher than 125/75 mm Hg should be achieved. Art.

Choice of drugs

Treatment of hypertension in diabetes mellitus should begin with angiotensin-converting enzyme inhibitors (ACEIs). Their effectiveness has been proven by international studies.

If ACE inhibitors are insufficiently effective, calcium antagonists (amlodipine, felodipine) are added to therapy. This combination protects the heart from the harmful effects of excess glucose.

If necessary, ACE inhibitors can be combined with diuretics. Preference should be given to indapamide, as the most neutral drug of all diuretics.

If arterial hypertension in patients with diabetes mellitus is combined with coronary heart disease (angina pectoris, previous heart attack), beta blockers should be added to treatment. You need to choose those that do not affect carbohydrate metabolism. These medications include cardioselective beta blockers, in particular bisoprolol, carvedilol, nebivolol. These medications should be used to prevent heart attack and sudden death.

The main groups of drugs used in the treatment of patients with arterial hypertension and diabetes mellitus	Drug names
ACE inhibitors
	Indapamide, Arifon
	Amlodipine, Felodipine
Beta blockers	Bisoprolol, Carvedilol, Nebivalol
Angiotensin-11 receptor blockers

The choice of medication also depends on its effect on kidney function. It has been proven that ACE inhibitors and indapamide reduce protein excretion in the urine and thereby prevent the development of renal failure; calcium antagonists (and diltiazem) have the same effect. These drugs can also be used in the complex treatment of hypertension in diabetes. In case of ACEI intolerance, angiotensin II receptor blockers (valsartan) are prescribed.

The effect of medications on the general condition

Some medications for hypertension have a negative effect on carbohydrate metabolism, so their use is not recommended for diabetes. This also applies to beta-blockers.

The most commonly used thiazide diuretic is hypothiazide. It may cause an increase in fasting blood glucose levels and glycosylated hemoglobin concentrations. While taking it, tolerance () to glucose worsens. There are cases where non-ketonemic hyperosmolar coma developed while taking hypothiazide. This is due to the suppression of insulin secretion and a decrease in tissue sensitivity to this hormone.

Beta-blockers also have an adverse effect on the course of diabetes. These drugs:

• inhibit insulin production;
• increase tissue resistance to it (insulin resistance);
• suppress the absorption of sugar by cells;
• increase the secretion of growth hormone - an insulin antagonist.

As a result, fasting and postprandial glucose levels increase. Cases of diabetic coma have been reported.

Beta blockers mask the symptoms of low blood glucose, making it difficult to diagnose hypoglycemia. They also inhibit the emergency release of carbohydrates from the liver, for example, during physical activity. This leads to more frequent development of hypoglycemic conditions.

Medicines from this group such as propranolol (obzidan), nadolol and timolol are contraindicated for people with diabetes. The use of high doses (more than 25 mg) of atenolol and metoprolol is extremely undesirable.

Studies have shown that even in individuals with normal blood glucose levels, long-term treatment with thiazides and beta blockers has a higher risk of developing diabetes than treatment with ACE inhibitors.

Prevention of hypertension in diabetes

To avoid severe complications of these diseases, the patient should reduce salt intake and increase physical activity. Walking for 20 to 30 minutes per day or any vigorous outdoor activity for 90 minutes per week is recommended. It is advisable to avoid using the elevator and using a car where you can walk.

It is important to follow a low-calorie diet, limiting the intake of salt, sugar, meat and fatty dairy products. These measures are aimed at treating obesity. Excess weight is an important factor in the onset and progression of diabetes. Normalizing body weight improves tissue absorption of glucose and causes a significant decrease in blood pressure.

• eat more vegetables and fruits;
• consume only low-fat dairy products;
• avoid salty and fried foods, use steaming or baking more often;
• eat whole grain bread, brown rice, pasta made only from durum wheat;
• reduce the amount of food you eat;
• be sure to have breakfast.

Often, people with diabetes experience “masked” hypertension, which is not detected with rare measurements, but has a bad effect on the condition of blood vessels. Therefore, all patients with diabetes need to regularly monitor 24-hour blood pressure. Drug treatment should be started when the normal levels are slightly exceeded.

People with diabetes should measure blood pressure not only while sitting, but also while standing. This helps to recognize orthostatic hypotension in time, requiring a reduction in the dose of antihypertensive drugs. It is necessary to monitor the level of cholesterol in the blood and prescribe medications to reduce it in time.

Diabetes mellitus is often complicated by hypertension or secondary arterial hypertension. The combination of these two diseases increases the risk of complications from the heart, kidneys, eyes, brain and other organs. To avoid this, you need to monitor your activity regimen, diet, get examined on time and take medications prescribed by your doctor.

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