Discontinue sulfonylurea because of Risk of hypoglycemia.

A 49-year-old man who consults for severe polyuria and polydipsia and unintentional weight loss of 10 kg and is diagnosed with diabetes mellitus due to a plasma blood glucose of 322 mg/dL and a glycosylated hemoglobin of 9.8%. His physician gave him dietary recommendations, the convenience of physical exercise, and he started treatment with metformin 850 mg/12 hours and glimepiride 6 mg/day. In the following weeks the glycemic controls are progressively reduced. At 4 months glycemia is 94 mg/dL and HbA1c is 5.9%. The patient complains of frequent episodes of dizziness, epigastric pain, blurred vision, sweating and tremor, which improve with food and occur mainly in the late morning and late afternoon. What modification would you propose in his treatment?

Review dietary carbohydrate distribution.

Substitute metformin with a DPP4 inhibitor.

[Sequential treatment with insulin glargine and metformin, and exenatide in a patient with newly diagnosed type-2 diabetes].

HISTORY AND ADMISSIONS FINDINGS: A 54-year-old man was admitted to hospital for treatment of a newly diagnosed type 2 diabetes. He had polydipsia and polyuria and had lost 11 kg in weight over four weeks. Further diagnoses were visceral obesity and arterial hypertension. Laboratory tests revealed highly elevated blood glucose parameters (HbA1c 14,9 %, fasting glucose 280 mg/dl, maximal postprandial glucose 430 mg/dl and 320 mg/dl before the meal) and triglyceride (2219 mg/dl). The patient was initially treated with a combination of insulin glargine and metformin. After a few days exenatide was added, as the patient wanted to be able to go without insulin. He was given a structured diabetes education and motivated to have five to six hours' of physical activity and a low glycemic diet. After a few days normal glucose levels had been achieved. After one month the insulin treatment was discontinued. The continuing treatment with metformin, 1000 mg twice daily, and exenatide, 5 mg twice daily, prolonged remission of beta-cell dysfunction and maintained normal blood glucose levels for seven months. After reduction of the metformin dosage (500 mg twice daily) and discontinuance of exenatide as well as a reduction of his physical activity (because of joint pain) for six months, the glucose control worsened. When exenatide was administered again, good control of postprandial blood glucose, but not of fasting glucose was achieved. Initial combination treatment with insulin glargine, metformin and exenatide may be beneficial in a subgroup of patients with newly diagnosed type 2 diabetes, markedly elevated blood glucose and free fatty acid levels (glucolipotoxicity). This should be further investigated in randomized controlled trials.

[Therapeutic behavior to follow in the following clinical case: treatment of type 2 diabetes].

A 62-year old woman with obesity, high blood pressure and type 2 diabetes mellitus (DM2) was referred to a Vascular Risk Unit of the Internal Medicine Department due to elevated HbA1C (8.1%) in spite of having taken metformin (850 mg/12h) and glipizide (10 mg/12 h) regularly. She tries to exercise daily (walking 30 min) and has lost weight (from 5 to 12 kg) several times, but always regains what she has lost. Furthermore, she monitors her glucose levels in fasting every two weeks and generally has between 120 and 160 mg/dL. Her high blood pressure is being treated with enalapril/HCTZ and she also takes aspirin 100mg/day and simvastatin 20 mg/day. It is seen in her family background that one brother died suddenly at 50 years of age. Her physical examination shows a BMI of 32.4 Kg/m(2), and she has no edemas in the lower limbs. Her BP is 154/82 mmHg and creatinine 0.9 mg/dL. She has no microalbuminuria and her liver function is normal. What treatment do you think would be the more appropriate? 1 - Add glitazones. 2 - Add incretin mimetics (GLP 1/ DPP-4). 3 - Slow acting insulin.

Efficacy and safety of the dipeptidyl peptidase-4 inhibitor, sitagliptin, in patients with type 2 diabetes mellitus inadequately controlled on glimepiride alone or on glimepiride and metformin.

To assess the efficacy and safety of a 24-week treatment with sitagliptin, a highly selective once-daily oral dipeptidyl peptidase-4 (DPP-4) inhibitor, in patients with type 2 diabetes who had inadequate glycaemic control [glycosylated haemoglobin (HbA(1c)) >or=7.5% and <or=10.5%] while on glimepiride alone or in combination with metformin. After a screening, diet/exercise run-in and drug wash-off period, a glimepiride +/- metformin dose titration/stabilization period and a 2-week, single-blind placebo run-in, 441 patients (of ages 18-75 years) were randomized to receive the addition of sitagliptin 100 mg once daily or placebo in a 1 : 1 ratio for 24 weeks. Of these patients, 212 were on glimepiride (>or=4 mg/day) monotherapy and 229 were on glimepiride (>or=4 mg/day) plus metformin (>or=1,500 mg/day) combination therapy. Patients exceeding pre-specified glycaemic thresholds during the double-blind treatment period were provided open-label rescue therapy (pioglitazone) until study end. The primary efficacy analysis evaluated the change in HbA(1c) from baseline to Week 24. Secondary efficacy endpoints included fasting plasma glucose (FPG), 2-h post-meal glucose and lipid measurements. Mean baseline HbA(1c) was 8.34% in the sitagliptin and placebo groups. After 24 weeks, sitagliptin reduced HbA(1c) by 0.74% (p < 0.001) relative to placebo. In the subset of patients on glimepiride plus metformin, sitagliptin reduced HbA(1c) by 0.89% relative to placebo, compared with a reduction of 0.57% in the subset of patients on glimepiride alone. The addition of sitagliptin reduced FPG by 20.1 mg/dl (p < 0.001) and increased homeostasis model assessment-beta, a marker of beta-cell function, by 12% (p < 0.05) relative to placebo. In patients who underwent a meal tolerance test (n = 134), sitagliptin decreased 2-h post-prandial glucose (PPG) by 36.1 mg/dl (p < 0.001) relative to placebo. The addition of sitagliptin was generally well tolerated, although there was a higher incidence of overall (60 vs. 47%) and drug-related adverse experiences (AEs) (15 vs. 7%) in the sitagliptin group than in the placebo group. This was largely because of a higher incidence of hypoglycaemia AEs (12 vs. 2%, respectively) in the sitagliptin group compared with the placebo group. Body weight modestly increased with sitagliptin relative to placebo (+0.8 vs. -0.4 kg; p < 0.001). Sitagliptin 100 mg once daily significantly improved glycaemic control and beta-cell function in patients with type 2 diabetes who had inadequate glycaemic control with glimepiride or glimepiride plus metformin therapy. The addition of sitagliptin was generally well tolerated, with a modest increase in hypoglycaemia and body weight, consistent with glimepiride therapy and the observed degree of glycaemic improvement.

Glimepiride: evidence-based facts, trends, and observations (GIFTS). [corrected].

Type 2 diabetes mellitus is characterized by insulin resistance and progressive β cell failure; therefore, β cell secretagogues are useful for achieving sufficient glycemic control. Glimepiride is a second-generation sulfonylurea that stimulates pancreatic β cells to release insulin. Additionally, is has been shown to work via several extra pancreatic mechanisms. It is administered as monotherapy in patients with type 2 diabetes mellitus in whom glycemic control is not achieved by dietary and lifestyle modifications. It can also be combined with other antihyperglycemic agents, including metformin and insulin, in patients who are not adequately controlled by sulfonylureas alone. The effective dosage range is 1 to 8 mg/day; however, there is no significant difference between 4 and 8 mg/day, but it should be used with caution in the elderly and in patients with renal or hepatic disease. In clinical studies, glimepiride was generally associated with lower risk of hypoglycemia and less weight gain compared to other sulfonylureas. Glimepiride use may be safer in patients with cardiovascular disease because of its lack of detrimental effects on ischemic preconditioning. It is effective in reducing fasting plasma glucose, post-prandial glucose, and glycosylated hemoglobin levels and is a useful, cost-effective treatment option for managing type 2 diabetes mellitus.

[A combination of dipeptidyl peptidase-4 inhibitor and metformin in the treatment of patients with type 2 diabetes mellitus: effective control of glycemia, weight, and quantitative body composition].

To study the impact of intensified therapy with the dipeptidyl peptidase-4 (DPP-4) inhibitor vilagliptin or sulfonylurea (SU) on the control of glycemia, weight, and quantitative body composition in patients with type 2 diabetes mellitus (DM-2) who have failed to achieve compensation during metformin monotherapy. Forty patients (mean age 55.0 (range 53.0-60.7) years; disease duration 2.0 (range 1.1-5.0) years) with poor glycemic control (7%<HbA1c <10%) during metformin monotherapy were allocated to 2 groups for 6-month therapy. In group 1 (n=20), vildagliptin 100 mg/day was added to metformin; in Group 2 (n=20), the latter was added by SU with its dose adjustment. Dual-energy X-ray absorptiometry was used to quantify body composition at baseline and after 6 months. The efficiency of glycemic control and adiponectin level changes was evaluated at baseline and after 3 and 6 months. Following 6 months of treatment, both groups achieved a comparable reduction in HbA1c levels; however, the number of glycemic episodes during SU treatment was found to be significantly higher. When vildagliptin was used in combination therapy, with the lean body mass being preserved, there was a statistically significant decrease in total body weight, body mass index (BMI), fat mass, and tissue fat percentage without considering bone mass, as well as waist circumference (WC), which was attended by an elevation of adiponectin levels. On the contrary, when SU therapy was intensified, total body weight, fat mass, BMI, and WC were statistically significantly increased and adiponectin levels remained unchanged. The glucose-lowering efficiency of combination therapy with metformin + vildagliptin, a DPP-4 inhibitor, was comparable with that of a metformin + SU combination, but safer with respect to the risk of developing hypoglycemia. Addition of vildaglptin to metformin monotherapy may cause an additional favorable effect in reducing body weight at the expense of a fat component, with the lean body mass being preserved, and in elevating the level of adiponectin, an adipose tissue-derived antiatherogenic hormone.

Rationale, design and baseline characteristics of a 4-year (208-week) phase III trial of empagliflozin, an SGLT2 inhibitor, versus glimepiride as add-on to metformin in patients with type 2 diabetes mellitus with insufficient glycemic control.

Sulfonylureas (SUs) are commonly used in the treatment of type 2 diabetes (T2DM), usually as second-line treatment after the failure of metformin. However, SUs are associated with poor durability, hypoglycemia and weight gain. Empagliflozin is a sodium glucose cotransporter 2 (SGLT2) inhibitor in development for the treatment of T2DM. In Phase II/III trials, empagliflozin reduced hyperglycemia, body weight and blood pressure, with a low incidence of hypoglycemia. The aim of this Phase III study is to compare the effects of empagliflozin and the SU glimepiride as second-line therapy in patients with T2DM inadequately controlled with metformin immediate release (IR) and diet/exercise. After a 2-week placebo run-in, patients were randomized to receive empagliflozin 25 mg once daily (qd) or glimepiride 1-4 mg qd double-blind for 2 years, in addition to metformin IR. Patients who participate in the initial 2-year randomization period will be eligible for a 2-year double-blind extension. The primary endpoint is change from baseline in HbA1c. Secondary endpoints are change from baseline in body weight, the incidence of confirmed hypoglycemia and changes in systolic and diastolic blood pressure. Exploratory endpoints include markers of insulin secretion, body composition and responder analyses. Safety endpoints include the incidence of adverse events (AEs) (including macro- and microvascular adverse events) and changes from baseline in clinical laboratory parameters. Between August 2010 and June 2011, 1549 patients were randomized and 1545 patients were treated. At baseline, mean (SD) age was 55.9 (10.4) years, HbA1c was 7.92 (0.84)%, body mass index was 30.11 (5.59) kg/m², systolic blood pressure was 133.5 (15.9) mmHg and diastolic blood pressure was 79.5 (9.4) mmHg. This is the largest study to compare the efficacy and safety of an SGLT2 inhibitor with an SU in patients with T2DM inadequately controlled on metformin to date. In addition to determining the effects of these treatments on glycemic control over the long term, this study will investigate effects on beta-cell function, cardiovascular risk factors and markers of renal function/damage. The results will help to inform the choice of second-line treatment in patients with T2DM who have failed on metformin. Clinicaltrials.gov NCT01167881.

Combination Therapy with a Dipeptidyl Peptidase-4 Inhibitor, Sulfonylurea, and Metformin Markedly Improves HbA1c Levels in Japanese Patients with Type 2 Diabetes Mellitus.

Combination therapy with a dipeptidyl peptidase (DPP)-4 inhibitor and metformin or sulfonylurea results in substantial and additive glucose-lowering effects in patients with type 2 diabetes mellitus (T2DM). However, it is not known whether triple combination therapy with a DPP-4 inhibitor, metformin, and sulfonylurea has greater additive effects or synergic effects. In the present report, we investigated the effect of addition of sitagliptin, the first-in-class DPP-4 inhibitor, to ongoing metformin and sulfonylurea therapy in three female Japanese patients with T2DM who refused insulin therapy. Combined treatment with all three drugs resulted in marked improvements in HbA1c. In the first patient, HbA1c levels decreased from 11.1% to 6.1% after the addition of sitagliptin to metformin 1000 mg, glibenclamide, and miglitol, even though the dose of glibenclamide was decreased. HbA1c levels decreased similarly in the second patient, who was being treated with metformin and glibenclamide, from 7.9% to 6.0% after addition of sitagliptin and an increase in metformin to 2250 mg; this patient ceased glibenclamide because of hypoglycemia and instead was started on low-dose glimepiride. In the third patient, HbA1c levels decreased from 8.6% to 7.1% after addition of glimepiride to ongoing sitagliptin and metformin therapy. All three patients had refused insulin therapy, despite the fact that ongoing combination therapy had failed to achieve satisfactory glycemic control. Based on these results, it is likely that the addition of sitagliptin to metformin and at least a small dose of sulfonylurea may be effective in reducing HbA1c levels without weight gain. This triple combination therapy may prove useful in at least some patients who need initiation of insulin therapy.

Pioglitazone/glimepiride

Medical uses In the United States pioglitazone/glimepiride is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus who are already treated with a thiazolidinedione and sulfonylurea or who have inadequate glycemic control on a thiazolidinedione alone or a sulfonylurea alone. In the European Union pioglitazone/glimepiride is indicated for the treatment of people with type 2 diabetes mellitus who show intolerance to metformin or for whom metformin is contraindicated and who are already treated with a combination of pioglitazone and glimepiride. References External links Anti-diabetic drugs

Hyperglycemia

In diabetes mellitus (by far the most common cause of chronic hyperglycemia), treatment aims at maintaining blood glucose at a level as close to normal as possible, in order to avoid serious long-term complications. This is done by a combination of proper diet, regular exercise, and insulin or other medication such as metformin, etc. Those with hyperglycaemia can be treated using sulphonylureas or metformin or both. These drugs help by improving glycaemic control. Dipeptidyl peptidase 4 inhibitor alone or in combination with basal insulin can be used as a treatment for hyperglycemia with patients still in hospital. Increasing aerobic exercise to at least 30 minutes will make better use of glucose accumulated in the body since glucose is being used for energy by the muscle. Calorie restriction would be one of the main lifestyle changes because it reduces over eating which contributes to hyperglycemia.

Comparative efficacy of glimepiride and/or metformin with insulin in type 2 diabetes.

The data regarding comparison of efficacy of metformin with glimepiride, newest Sulfonylurea, or with the use of both drugs in combination with insulin is rare in the literature. Therefore, we assessed the daily insulin dose, hypoglycemic events and body weight on achieving desirable glycemic control after addition of insulin, to glimepiride 8 mg and/or metformin 2500 mg, in subjects with type 2 DM manifesting lapse of glycemic control. S.C. insulin Novolog Mix [70/30], pre-supper was initiated in 12 subjects on metformin, 14 subjects on glimepiride, and 12 subjects receiving both drugs, with HbA1C > 7.5% and eight subjects receiving placebo. Insulin dose was increased by 4 U at weekly interval until fasting blood sugar [FBS] between 6.6 and 8 mM/l was attained and then further titrated by 2 U every week to attain and maintain FBS between 4.5 and 6.7 mM/l over the next 4 months. The comparisons were conducted between these groups for HbA1C, the daily insulin dose, body weight noted at the end of this study period as well as the hypoglycemic episodes per patient during the last 4 weeks of the study period. HbA1C levels were < 7.0% in all subjects at the end of the study. The daily insulin dose (units), total and per kg/BW was significantly lower [p < 0.001] with metformin (51 +/- 5, 0.51 +/- 0.10), glimepiride (40 +/- 4, 0.42 +/- 0.09) as well as with both drugs (23 +/- 7, 0.21 +/- 0.07) in comparison to placebo (82 +/- 10, 0.82 +/- 0.12). The insulin dose was also significantly lower [p < 0.05] in subjects on both drugs than subjects receiving them individually. Weight gain was less [p < 0.001] with metformin [2.5 +/- 0.74 kg], glimepiride [2.3 +/- 0.7 kg], and both drugs [2.2 +/- 0.61 kg] in comparison to placebo [5.2 +/- 1.4 kg] whereas the hypoglycemic episodes were lesser with metformin (3.8 +/- 1.2) and glimepiride (3.3 +/- 0.9) and least with both drugs (2.5 +/- 0.6) in comparison to placebo (5.2 +/- 1.0). Glimepiride and metformin are effective individually in achieving a glycemic goal with a less daily insulin dose, weight gain, and hypoglycemic episodes in comparison to insulin monotherapy in subjects with type 2 diabetes mellitus with further marked reduction in these parameters when used concurrently.

Glycemic control: a combination of lifestyle management and the use of drugs.

Some 30% of contemporary cardiology patients have coexisting known diabetes, and another 40% have either undiagnosed diabetes or prediabetes. There is still no final conclusive evidence of cardiovascular benefit by good glycemic control in type 2 diabetes, although studies like the United Kingdom Prospective Diabetes Study (UKPDS) and the Prospective Pioglitazone Clinical Trial in Macrovascular Events, and meta-analyses based on these and other randomized controlled trials of blood glucose-lowering therapies have been encouraging. On the other hand, microvascular disease is clearly reduced by good glycemic control. Structured education has remained a mandatory prerequisite of any successful treatment. Not only is appropriate weight management by diet and exercise able to revert new onset diabetes to normal, but it is also the foundation of any successful pharmacotherapy of diabetes. Aiming at normal fasting plasma glucose concentrations of 5.3 mmol/L or 95 mg/dL appears to be safe since publication of the long-term outcome results of the Outcome Reduction with an Initial Glargine INtervention trial. Individualized target glycosylated hemoglobin levels as near to normal as safely possible (i.e., <7% and avoiding hypoglycaemia) are the goal for glycemic control. Hypoglycemia seems to emerge as a real concern in cardiology patients. Based on the findings of UKPDS, including the "legacy" study, metformin is the most widely recommended first-line drug therapy in type 2 diabetes, also in terms of preventing cardiovascular complications. An alternate first-line option in some parts of the world, especially Asian countries, is the class of alpha-glucosidase inhibitors. In most patients, combination therapies with two or three classes of drugs are warranted. Early combination are the golden strategy as type 2 diabetes is a multi-causal disease; the various classes of drugs have distinct and synergistic modes of action, and the blood glucose-lowering efficacy of these drugs is more or less fully maintained in combination. The recent joint American Diabetes Association/European Association for the Study of Diabetes position statement mentions five options as step two of the treatment algorithm for combination with metformin: sulfonylureas, pioglitazone, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 agonists, and basal insulin.

Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group.

Treatment with diet alone, insulin, sulfonylurea, or metformin is known to improve glycemia in patients with type 2 diabetes mellitus, but which treatment most frequently attains target fasting plasma glucose (FPG) concentration of less than 7.8 mmol/L (140 mg/dL) or glycosylated hemoglobin A1c (HbA1c) below 7% is unknown. To assess how often each therapy can achieve the glycemic control target levels set by the American Diabetes Association. Randomized controlled trial conducted between 1977 and 1997. Patients were recruited between 1977 and 1991 and were followed up every 3 months for 3, 6, and 9 years after enrollment. Outpatient diabetes clinics in 15 UK hospitals. A total of 4075 patients newly diagnosed as having type 2 diabetes ranged in age between 25 and 65 years and had a median (interquartile range) FPG concentration of 11.5 (9.0-14.4) mmol/L [207 (162-259) mg/dL], HbA1c levels of 9.1% (7.5%-10.7%), and a mean (SD) body mass index of 29 (6) kg/m2. After 3 months on a low-fat, high-carbohydrate, high-fiber diet, patients were randomized to therapy with diet alone, insulin, sulfonylurea, or metformin. Fasting plasma glucose and HbA1c levels, and the proportion of patients who achieved target levels below 7% HbA1c or less than 7.8 mmol/L (140 mg/dL) FPG at 3, 6, or 9 years following diagnosis. The proportion of patients who maintained target glycemic levels declined markedly over 9 years of follow-up. After 9 years of monotherapy with diet, insulin, or sulfonylurea, 8%, 42%, and 24%, respectively, achieved FPG levels of less than 7.8 mmol/L (140 mg/dL) and 9%, 28%, and 24% achieved HbA1c levels below 7%. In obese patients randomized to metformin, 18% attained FPG levels of less than 7.8 mmol/L (140 mg/dL) and 13% attained HbA1c levels below 7%. Patients less likely to achieve target levels were younger, more obese, or more hyperglycemic than other patients. Each therapeutic agent, as monotherapy, increased 2- to 3-fold the proportion of patients who attained HbA1c below 7% compared with diet alone. However, the progressive deterioration of diabetes control was such that after 3 years approximately 50% of patients could attain this goal with monotherapy, and by 9 years this declined to approximately 25%. The majority of patients need multiple therapies to attain these glycemic target levels in the longer term.

Evaluation of efficacy and tolerability of glimepiride and metformin combination:  a multicentric study in patients with type-2 diabetes mellitus, uncontrolled on monotherapy with sulfonylurea or metformin.

The objectives of this study were to evaluate the efficacy and tolerability of glimepiride plus extended release metformin (MET) on glycemic control in patients with type-2 diabetes mellitus uncontrolled on monotherapy with sulfonylurea or MET. This was a prospective, open-labeled, multicentric study over 12 weeks. Patients who were diagnosed with type-2 diabetes and were uncontrolled on monotherapy with single oral hypoglycemic agents such as glimepiride or MET and characterized by glycosylated hemoglobin (HbA1c) ≥7% and ≤10% and fasting plasma glucose (FPG) ≥ 140 mg/dL were enrolled in this study. Treatment regimen was started at 1 mg of glimepiride plus 500 mg of MET once a day and was titrated to next dose level depending on the clinician's judgment, not exceeding a total daily dose of 8 mg of glimepiride and 2000 mg of MET. After 12-weektreatment, glimepiride plus MET combination showed improvement in metabolic control as assessed by changes in HbA1c, FPG, and post prandial glucose (PPG). Primary efficacy parameter, HbA1c, was significantly reduced to (7.65 ± 1.70) at the end of the treatment from the baseline value (8.35 ± 0.93) (P < 0.001). Of the patients, 65.79% showed ≥0.5% reduction in HbA1c and or HbA1c <7% at the end of the therapy. FPG and PPG were significantly reduced at the end of the therapy as compared with baseline values (P < 0.001). Moreover, the lipid profile was also improved during the treatment period. The addition of glimepiride to MET is an effective treatment for patients inadequately controlled on sulfonylurea or Met alone. A combination of glimepiride with MET achieves good glycemic control with better tolerability profile.

[Starting insulin or not? And if so, which basal insulin?]

A 55-year-old patient with a BMI of 30 kg/m2 is referred for uncontrolled type 2 diabetes mellitus. His HbA1c-concentration is 71 mmol/mol, despite an initial 8% weight loss and treatment with metformin and glimepiride. The general practitioner proposes to start with insulin, but the patient refuses. We discuss whether there is a good alternative for insulin such as more weight loss and the addition of more drugs. Our patient then changes his mind and agrees to start insulin treatment. Basal insulin is usually recommended in cases like this.Since there are no significant differences between different types of available basal insulin, it seems reasonable to take price into account. Our patient achieved reasonable glucose control without weight gain using a combination of basal insulin and a GLP-1 receptor agonist.

Gemigliptin

Glycemic variability and chronic sustained hyperglycemia are the main components of dysglycemia in diabetes. The previous studies suggested that different pharmacodynamic profiles between DPP-4 inhibitors have been associated with the different effects on glycemic variability. In this study, a multicenter, randomized, active-controlled, parallel group, open-label, exploratory study was designed to evaluate the efficacy on glycemic variability and safety of initial combination therapy of gemigliptin 50 mg qd versus sitagliptin 100 mg qd, or glimepiride 2 mg qd with metformin in patients with T2DM (study identifier: LG-DPCL012, STABLE study; ClinicalTrials.gov registration number: NCT01890629). The mean amplitude of glycemic excursions (MAGE) and SD of glucose were used for assessing glucose fluctuations from the baseline after 12 weeks of treatment. At 12 weeks, MAGE was significantly lower in the DPP-4 inhibitor groups (gemigliptin and sitagliptin) than in the glimepiride group

[Treatment of elderly diabetic patients].

Type 2 diabetes has become a pandemic disease over the past 50 years. Its incidence increases the most rapidly in the senior population, i.e. among people older than 65. In a number of countries 1/4 of the people with diabetes are now older than 65 years. Geriatrics now examines numerous differences regarding the senior patients, which often lead to somewhat different therapeutic procedures as compared to the treatment of other adult patients. This paper aims to show some different aspects of the treatment of an elderly patient with diabetes. The intensity of diabetes treatment in the elderly is mainly defined by the incidence of symptoms caused by diabetic decompensation which negatively affect quality of life and are likely to increase mortality. The treatment goals expressed by HbA1c, fasting and post-prandial glycemia, should be set individually based on age, initial HbA1c, present comorbidities and the level of frailty of an elderly patient. An effort to reduce weight regarding people at an older age is probably inappropriate and maybe even harmful, while physical activity reduces mortality and slows muscle catabolism at every age. Ideal is normal walking for 20-30 minutes a day. Except for "very fit elders" without renal insufficiency, the sulfonylurea treatment is unsuitable and perhaps even harmful. It significantly increases the incidence of different types of hypoglycemia and very likely overall mortality as well. The basis of diabetes treatment for the elderly is the effort to perform any regular exercise. In regard to medication treatment it is recommended to choose metformin or gliptin following the rule "start low, go slow", i.e. start with low medication doses and increase them at a slow pace. The main goal of the treatment is to maintain the good quality of life as long as possible, without symptoms associated with hyperglycemia with minimizing the risk of hypoglycemia development.

Probable hypoglycemic adverse drug reaction associated with prickly pear cactus, glipizide, and metformin in a patient with type 2 diabetes mellitus.

To report a case of an adverse drug reaction (ADR) in a patient with type 2 diabetes mellitus taking prickly pear cactus (PPC), glipizide, and metformin. A 58-year-old Mexican male with type 2 diabetes mellitus being treated with metformin 1000 mg twice daily and extended-release glipizide 10 mg daily was referred to the pharmacist for medication education. He denied taking herbal supplements or experiencing hypoglycemia. Two hemoglobin A(1c) values (6.8% and 6.7%) obtained over the past year demonstrated glycemic control, which was supported by his reported fasting blood glucose readings of 113-132 mg/dL. One month later, the patient reported 4 hypoglycemic events with blood glucose readings of 49-68 mg/dL, which resulted in discontinuation of glipizide. One month later, the patient denied any further hypoglycemia. During medication reconciliation he reported consuming crude PPC pads daily for 2 months for glucose control. Literature suggests that PPC has an effect on lowering blood glucose levels in patients with type 2 diabetes mellitus, although few identified data describe ADRs from combining PPC with other agents used in treating type 2 diabetes mellitus. A literature search of MEDLINE (through December 2009) using the search terms diabetes mellitus, prickly pear cactus, nopal, opuntia, metformin, glipizide, glyburide, glimepiride, and sulfonylurea revealed no case reports of the described ADR. One case report describing the blood glucose-lowering effect of PPC in a patient concurrently taking oral antihyperglycemics documented an episode of hypoglycemia, although the Naranjo probability scale was not applied. One patient survey discovered the most common drug-herbal interaction in the given population to be between PPC and antihyperglycemic agents, resulting in hypoglycemia. In our case, use of the Naranjo probability scale suggests the ADR to be probable. The mechanism may be due to the additive glucose lowering of the 3 agents consumed concurrently by the patient. Patients with type 2 diabetes mellitus should be routinely counseled about the use of herbal products to minimize the risk of ADRs.

[Towards new recommendations for the treatment of type 2 diabetes? An expert's point of view].

Type 2 diabetes is growing rapidly, as its cost and the daily concern of general practitioners. Many treatment advances are now available and many more are in development. Currently the drugs based on the "incretin" phenomenon are the more recent and innovative (tree different DPP-inhibitors and two GLP1 analogues) with a specific benefit, no hypoglycemic attacks and a better body weight control. Thus the recommendations for the management of hyperglycaemia are becoming increasingly complex and difficult to write. The first recommendation is to not drift HbAlc, the second, is to use metformin as first line treatment for most patients in the absence of intolerance. The delay in passing to combination (two 0ADs) remains excessive; it must be done without delay at 6.5 or 7% HbA1c. There are four possible combinations today (acarbose, sulfonylureas, gliptins, glitazones). Then, one can choose between triple oral therapy, insulin and GLP1 analogues. Deciding who needs what becomes more difficult regarding the different phenotypes and specificities of each patient, the economic considerations and the benefit/risk of the different classes or strategies. Thereby, recommendations cannot enter so many details and strategies. The need for continuing medical education and the referral to diabetologist more often is becoming essential.

InternalMed_Harrison

Considerable clinical experience exists with metformin and sulfonylureas because they have been available for several decades. It is assumed that the α-glucosidase inhibitors, GLP-1 agonists, DPP-IV inhibitors, thiazolidinediones, and SLGT2 inhibitors will reduce DM-related complications by improving glycemic control, but longterm data are not yet available. The thiazolidinediones are theoretically attractive because they target a fundamental abnormality in type 2 DM, namely insulin resistance. However, all of these agents are currently more costly than metformin and sulfonylureas. Patient with type 2 diabetes Individualized glycemic goal Medical nutrition therapy, increased physical activity, weight loss + metformin

Diabetes mellitus in the young: Gliptins or sulfonylurea after metformin?

Diagnosis and initial management of diabetes mellitus (DM) in the young are clinical dilemma. Gliptins may be a safer and more effective option than sulfonylureas. Few Indian studies have addressed this issue of clinical relevance. To compare the use of sitagliptin and glimepiride as early add-on drugs along with metformin in young patients with DM to achieve optimum glycemic targets. This was a prospective, open-label, cohort study set in a tertiary care hospital in North India. Newly diagnosed patients of DM ≤35 year of age were initially treated to pre-defined glycemic goals (Fasting plasma glucose (FPG) 70-130, post prandial glucose (PPG) < 180 mg/dl) with insulin and metformin 1 g for 8 weeks. Insulin was discontinued and metformin increased to 2 g daily for next 4 weeks. Thereafter, glimepiride 1 mg or sitagliptin 100 mg was randomly added to those who were not maintaining the set glucose targets. Dose of glimepiride was uptitrated every 4 weeks upto a maximum of 4 mg. Three groups (Gp A: Metfromin 2 g/d, Gp B: Metformin 2 g + Glimepiride 1-4 mg/d, and Gp C: Metformin 2 g + sitagliptin 100 mg/d) were followed up over next 24 weeks. They were compared for glycemic control and weight change. Those failing therapy on these drugs (FPG > 180, PPG > 250 mg/dl with/without catabolic symptoms/ketosis) were withdrawn. Sitagliptin with metfromin and metfromin alone group fared better than the glimepiride group for glycemic control, lesser treatment failures, and less weight gain. In this limited study, we found that sitagliptin is a safer and more effective option in young, newly diagnosed patients with DM. Findings of this study are relevant for clinical practice in Indian setting.

[Management of type 2 diabetes: new or previous agents, how to choose?].

Once lifestyle measures implemented, if hyperglycemia persists, above individual HbA1c targets, a medication should be started in type 2 diabetic patients (T2DM). First, unless exception, an oral antidiabetic drug. Except in case of intolerance, the initial monotherapy, metformin remains the strengthening treatment. Latter, combination of two oral drugs, now offers several options, mainly the choice to associate a "conventional insulin-secretor", sulfonylureas, glinide, or a "new one" belonging the class of "incretin", more readily a gliptine (DPP-4 inhibitors) rather than injectable GLP-1 analogue which can also be sometimes chosen at this stage. These options are mostly new and have the advantage a neutral or favourable (for GLP-1) effect on body weight in obese type 2 DM patient and the absence of any hypoglycaemic risk in both classes of incretins. But this risk varies depending on the patient profile, much higher if the target HbA1c is low (6 to 6.5 or 7%), or in the elderly, fragile and/or in case of renal insufficiency. These two different situations with a high risk of hypoglycaemia, define best indications of this new class. If dual oral therapy does not achieve the goals we are faced with three options: triple oral therapy: metformin-sulfonylurea-gliptine or one of two approaches with injections, insulin or GLP-1 analogues. The use of GLP-1 analogues is often delayed today and put wrongly in balance with the transition to insulin, a use already delayed in France and insufficient. The use of incretins is new and needs to be validated by studies of sustainability on glycemic control, prevention of microvascular and macrovascular complications and after years on the market security of use, primarily on the exocrine pancreas. In short, individualization of strategies and HbA1c targets are required, the new molecules can help us in this process. This individualization can easily be done through the handy guide proposed by the experts ADA EASD statement, endorsed by the SFD, abandoning the complex algorithm recently again proposed by HAS and ANSM in 2013. A recommendation that prioritizes the costs of the strategies. An absolutely critical issue, while admitting not to have the tools to measure them in all their dimensions. Finally, we must reconsider every treatment after a maximum of 6 months of use, if the results are deemed inadequate substitute rather than adding drugs.

Diabetes management

"Perfect glycemic control" would mean that glucose levels were always normal (70–130 mg/dl, or 3.9–7.2 mmol/L) and indistinguishable from a person without diabetes. In reality, because of the imperfections of treatment measures, even "good glycemic control" describes blood glucose levels that average somewhat higher than normal much of the time. In addition, one survey of type 2 diabetics found that they rated the harm to their quality of life from intensive interventions to control their blood sugar to be just as severe as the harm resulting from intermediate levels of diabetic complications. In the 1990s the American Diabetes Association conducted a publicity campaign to persuade patients and physicians to strive for average glucose and hemoglobin A1c values below 200 mg/dl (11 mmol/l) and 8%. Currently, many patients and physicians attempt to do better than that.

Diabetes

Diagnosis Diabetes mellitus is diagnosed with a test for the glucose content in the blood, and is diagnosed by demonstrating any one of the following: Fasting plasma glucose level ≥ 7.0 mmol/L (126 mg/dL). For this test, blood is taken after a period of fasting, i.e. in the morning before breakfast, after the patient had sufficient time to fast overnight. Plasma glucose ≥ 11.1 mmol/L (200 mg/dL) two hours after a 75 gram oral glucose load as in a glucose tolerance test (OGTT) Symptoms of high blood sugar and plasma glucose ≥ 11.1 mmol/L (200 mg/dL) either while fasting or not fasting Glycated hemoglobin (HbA1C) ≥ 48 mmol/mol (≥ 6.5 DCCT %).

[Oral antidiabetic therapy].

Consistent antihyperglycaemic treatment for preventing vascular complications in type 2 diabetes mellitus (2DM) often require the application of several measures. The basis of such treatment should be dietary changes and increased physical exercise. The target of antiglycemic treatment is the reduction of HbA1c to below 6.5%. Regular monitoring of HbA1c every 2-6 months is reasonable in order to recognize therapeutic failure early and adapt treatment accordingly. Metformin is the drug of first choice for the oral treatment of 2DM, once possible contraindications having been excluded. The advantage of glinides, compared with sulfonylureas, is mainly in allowing greater dietary flexibility. Although not finally decided, there are ever fewer objections against combined metformin and sulphonylurea treatment. The current guidelines of the (British)National Institute for Clinical Excellence (NICE) specifically recommend this combination treatment. There are pointers to glitazone having protective effects in 2DM beyond its blood-sugar lowering action. However, the clinical significance of these effects requires confirmation. If adequate blood-sugar reduction cannot be achieved with oral medication it is important to initiate insulin administration as soon as possible.

Clinical Review: Safety and Efficacy Comparison between Sulfonylureas and Dipeptidyl Peptidase-4 Inhibitors as Second-Line Therapies in Type 2 Diabetes Mellitus.

According to the World Health Organization (WHO), diabetes mellitus is considered the 7th leading cause of death as of 2016, while almost half of all deaths related to high blood glucose occur before the age of 70. According to the 2019 American Diabetes Association's (ADA) guidelines, metformin is the firstline treatment for patients with Type 2 diabetes. Additional therapy is dependent on multiple patient-specific factors, including cardiovascular risks, risk of hypoglycemia, metabolic changes, and cost. The objective of this systematic review is to analyze variables of interest in Type 2 diabetes including fasting blood glucose (FBG), post-prandial blood glucose (PPBG), hemoglobin A1c (HbA1c), microvascular complications, and cardiovascular outcomes in order to determine the shift towards the newer class of medications for type 2 diabetes. A systematic review was conducted using ScienceDirect as the primary source of obtaining articles. This review used PRISMA for reporting and GRACE for quality assessment of ten articles. The inclusion criteria for the review consisted of patients who were on metformin therapy for a sufficient amount of time, as defined by the trial's protocol, and who were then initiated on either a sulfonylurea (glipizide or glimepiride) or a DPP-4 inhibitor (saxagliptin or linagliptin). The articles included in this review range from 2005-2019 that are written in English only. Exclusion criteria for this systematic review were articles in which patients were not initially started on metformin therapy, were diagnosed with Type 1 diabetes mellitus, and articles that were written in languages other than English. After filtering 50 studies, 10 were selected for meeting the criteria of variables of interest. Findings suggested a significant reduction in fasting plasma glucose with 154 mg/dL + 4 mg/dL as baseline, decreasing to 132 mg/dL + 4 mg/dL with the use of glipizide & metformin combination. A similar pattern was presented with the use of saxagliptin and metformin in combination, but changes were less significant than glipizide. However, hypoglycemic events in patients who were taking glipizide with metformin versus saxagliptin with metformin; 13.4% of patients achieved HbA1c <7% without hypoglycemic events compared to 22.2% of the patients who achieved an HbA1c of <7% without hypoglycemic events. Despite the higher efficacious characteristics of sulfonylureas in lowering HbA1c, due to its reported hypoglycemic effects, DPP-4 inhibitors may be considered as a clinically stable choice for second-line therapy after completing maximally tolerated doses of metformin. Sulfonylureas are considered better than DPP-4 inhibitors for treatment in patients with cardiovascular disease history and hypoglycemia.

Effect of noninsulin antidiabetic drugs added to metformin therapy on glycemic control, weight gain, and hypoglycemia in type 2 diabetes.

Metformin is the recommended initial drug therapy for patients with type 2 diabetes mellitus (DM). However, the optimal second-line drug when metformin monotherapy fails is unclear. To determine the comparative efficacy, risk of weight gain, and hypoglycemia associated with noninsulin antidiabetic drugs in patients with type 2 DM not controlled by metformin alone. A literature search via MEDLINE (beginning in January 1950) and Cochrane CENTRAL through January 2010 and a manual search of references for additional relevant studies. Randomized controlled trials (RCTs) with at least 3 months' duration, evaluating noninsulin antidiabetic drugs added to metformin in patients experiencing an inadequate response to maximized and stable (> or = 4 weeks at > or = 1500 mg or maximally tolerated dose) metformin therapy. Inclusion/exclusion criteria; duration of patient follow-up; drug, dose, and schedule used; use of concurrent lifestyle modification; and baseline characteristics (age, sex, anthropometrics, glycated hemoglobin A(1c) [HbA(1c)], duration of DM, and metformin dose). End points collected included mean change in HbA(1c), proportion of patients achieving HbA(1c) goal of less than 7%, change in weight, and incidence of hypoglycemia. Mixed-treatment comparison meta-analysis was used to calculate the weighted mean difference for changes from baseline in HbA(1c) and body weight and relative risk (RR) of HbA(1c) goal attainment and hypoglycemia, with associated 95% credible intervals. Overall, 27 RCTs (n = 11 198) were included. Mean (range) trial duration was 32 (12-52) weeks. The different classes of drugs were associated with similar HbA(1c) reductions (range, 0.64%-0.97%) compared with placebo. Although use of thiazolidinediones, sulfonylureas, and glinides were associated with weight gain (range, 1.77-2.08 kg), glucagon-like peptide-1 analogs, alpha-glucosidase inhibitors, and dipeptidyl peptidase-4 inhibitors were associated with weight loss or no weight change. Sulfonylureas and glinides were associated with higher rates of hypoglycemia than with placebo (RR range, 4.57-7.50). When added to maximal metformin therapy, all noninsulin antidiabetic drugs were associated with similar HbA(1c) reductions but differed in their associations with weight gain and risk of hypoglycemia.

A novel cobiotic containing a prebiotic and an antioxidant augments the glucose control and gastrointestinal tolerability of metformin: a case report.

The gut microbiome plays an important role in regulation of metabolic processes, including digestion, absorption, and synthesis of bioactive molecules that signal physiological host mechanisms. Changes in the human gut microbiome are associated with type 2 diabetes and insulin resistance. Water-soluble dietary fibres like inulin and beta-glucan are fermented in the colon, and beta-glucan increases viscosity. Blueberries improve insulin sensitivity through an antioxidant effect. A cobiotic, consisting of purified inulin, sugar-free blueberry pomace extract, and an oat preparation of purified beta-glucan was developed for twice a day (bid) consumption as a smoothie drink to repair the gastrointestinal dysbiosis in type 2 diabetes. A 30-year-old man presented with new onset type 2 diabetes and a fasting glucose (FBS) of 375 mg/dl. Metformin 500 mg bid was initiated and increased to 1 g bid after 1 week. During the first 9 days of metformin treatment, he developed diarrhoea, but his FBS only dropped to 325 mg/dl. The cobiotic bid was added on the 9th day of metformin treatment, and after 2 days, his FBS dropped to 175 mg/dl. After 8 weeks on metformin and the cobiotic, his blood sugar was 100 mg/dl and he lost 5.5 kg. His stools became soft and formed on the cobiotic, reverted to diarrhoea when off of it for 2 days, and returned to normal on resuming the cobiotic formulation. Metformin is a safe, effective and inexpensive generic medication favouring weight loss, recommended as initial treatment of type 2 diabetes by the American Diabetes Association. However, a 20% incidence of diarrhoea limits its tolerability. A safe food supplement that can increase the efficacy of metformin and its tolerability, as occurred in this case report, would have significant positive public health consequences. A controlled clinical trial of the cobiotic with metformin is planned.

What are the preferred strategies for control of glycaemic variability in patients with type 2 diabetes mellitus?

The aim of therapy in type 2 diabetes in terms of blood glucose control is to reduce to target levels HbA1c and to reduce glycaemic variability in order to avoid both hypoglycaemia and wide excursions of postprandial glucose. The first approach to reduce glycaemic variability should consider a dietary and behavioural approach aiming to limit the glycaemic index and the glycaemic load of food and the prescription and implementation of a physical activity plan appropriate for the subject. From the pharmacological point of view, the diabetes specialist has now a much richer therapeutic armamentarium. The therapeutic algorithms can help the physician to choose the most appropriate drug. The traditional approach involves: i) metformin, acting mainly on fasting blood glucose; ii) sulphonylureas, that have shown a number of drawbacks, including the high risk of hypoglycemia; iii) pioglitazone, with a substantial effect on fasting and postprandial glucose and a low risk of hypoglycaemia; iv) insulin, that can be utilized with the basal or prandial approach. The new drugs belonging to the class of dipeptidyl peptidase-4 inhibitors have shown the reduction of postprandial glucose, a neutral effect on weight increase, a good safety profile and preliminary positive cardiovascular effects. When excess weight prevails, the glucagon-like peptide-1 agonists may be the preferred choice for their effect on weight reduction, reduction of hyperinsulinism and glycaemic variability.

Effects of replacing metformin with pioglitazone on glycemic control in japanese patients with poorly controlled type 2 diabetes mellitus: A 12-week, open-label, prospective study.

Insulin resistance is a critical aspect of the pathophysiology of type 2 diabetes mellitus and is also associated with other risk factors for cardiovascular disease (eg, dyslipidemia and hypertension). Accordingly, insulin resistance is a possible target for lowering plasma glucose concentration and preventing diabetic macroangiopathy. Biguanides, such as metformin, and thiazolidinediones (TZDs), such as pioglitazone, improve insulin resistance. The aims of this study were to assess the effects of replacing a biguanide with a TZD on glycemic control in patients with poorly controlled type 2 diabetes mellitus, and also to identify the factors affecting interpatient variation in the effects of treatment change. This was a 12-week, open-label, prospective study in which previously prescribed metformin (500 or 750 mg/d) was replaced with pioglitazone (15 or 30 mg/d) in patients with poorly controlled type 2 diabetes mellitus. Patients with a glycosylated hemoglobin (HbA1c) concentration >7% despite treatment with diet, exercise, and hypoglycemic agents other than TZDs were eligible for the study. Patients who never received TZDs were also eligible for inclusion. Vital signs, metabolic parameters, and arterial stiffness were assessed at baseline and after 12 weeks of treatment with pioglitazone. The primary end point was change in HbA1c concentration after replacing metformin with pioglitazone. Tolerability was assessed by medical history, physical examination, and laboratory tests (aspartate aminotransferase, alanine aminotransferase, and γ-glutamyl transpeptidase). Twenty-one Japanese patients (15 women, 6 men; mean [SD] age, 61.8 [8.4] years; body mass index, 25.5 [3.0] kg/m(2)) were included in the study. HbA1c concentration was not significantly changed from baseline after 12 weeks of pioglitazone treatment (8.0% [0.7%] vs 8.2% [0.7%]). Fasting plasma glucose (FPG) concentration also was not significantly changed after the replacement of treatment (156 [27] vs 144 [30] mg/dL). In addition, the resistin concentration did not change significantly from baseline after 12 weeks of pioglitazone treatment (6.6 [3.8] vs 6.4 [3.6] ng/mL). In contrast, significant improvement from baseline was observed in triglyceride (TG) concentrations (157 [109] vs 117 [68] mg/dL; P = 0.003), high-density lipoprotein cholesterol (HDL-C) (55 [12] vs 61 [16] mg/dL; P = 0.016), remnant-like particle cholesterol (6.6 [6.0] vs 5.3 [3.5] mg/dL; P = 0.048), and serum adiponectin (8.8 [4.3] vs 23.3 [11.7] μg/mL; P < 0.001). Pulse wave velocity was also significantly improved (1730 [361] vs 1622 [339] m/sec; P = 0.009). Changes in HbA1c were significantly correlated with serum fasting insulin concentration at baseline in the patients not receiving insulin preparations (r = -0.635, P = 0.013). The percentage change in serum adiponectin concentration was correlated with the percentage changes in HbA1c and FPG concentrations (HbA1c, r = -0.518, P = 0.019; FPG, r = -0.594, P = 0.006). Body weight was significantly increased after treatment (62.6 [11.9] vs 65.5 [12.2] kg; P < 0.001). Mild edema was reported in 5 patients. One patient discontinued treatment due to an increase in serum creatine kinase activity to ~6.6 times the upper limit of normal. Replacement of metformin with pioglitazone did not produce significant differences in HbA1c and FPG concentrations from baseline after 12 weeks of treatment in these patients with poorly controlled type 2 diabetes mellitus. However, the replacement was effective in a subset of patients whose serum insulin concentrations were high or whose serum adiponectin concentrations were sensitive to TZDs. In addition, the replacement was associated with significant improvements in TG, HDL-C, serum adiponectin concentration, pulse wave velocity, and body weight increase from baseline.

Impact of health policy and practice on finding the best fit for patients with type 2 diabetes after metformin failure: Croatian pilot study.

We assessed the impact of clinical practice and health policy on the choice and efficacy of different second-line therapies for the treatment of type 2 diabetes (T2DM) after failure of metformin. This retrospective database analysis included 200 patients with a follow-up period of 6 months. The primary end-point was achievement of HbA1c <7% and fasting (FBG) and postprandial glucose levels (PPG) <7.2mmol/L and <10mmol/L, respectively after three and six months of different add-on treatments. Secondary end-points were weight change during treatment and incidence of hypoglycemia. All second-line therapeutic options, except human basal insulin (BHI) and thiazolidendions (TZD) significantly increased the proportion of patients reaching target HbA1c after 6 months (p<0.01). Only sulfonylurea (SU) and dipeptidyl peptidase-4 (DPP-4) inhibitors significantly reduced all monitored parameters of glucoregulation without changing body weight and BMI after 3 and 6 months as opposed to insulin agents. However, there were no statistically significant differences between the groups when adjusting for starting HbA1c, FBG and PPG (F=1.16, p=NS), although a statistically significant difference in HbA1c levels (F=3.35, p<0.01) persisted in DPP-4 inhibitor users. The incidence of hypoglycemia was significantly higher in patients treated with NPH insulin and premixed insulin than in patients treated with other agents. A more aggressive approach is needed with early treatment intensification using available agents.

InternalMed_Harrison

Patient with type 2 diabetes Individualized glycemic goal Medical nutrition therapy, increased physical activity, weight loss + metformin Insulin + metformin Reassess HbA1c Reassess HbA1c Reassess HbA1c Combination therapy -metformin + second agent Combination therapy -metformin + two other agents FIGURE 418-3 Glycemic management of type 2 diabetes. See text for discussion of treatment of severe hyperglycemia or symptomatic hyperglycemia. Agents that can be combined with metformin include insulin secretagogues, thiazolidinediones, α-glucosidase inhibitors, DPP-IV inhibitors, GLP-1 receptor agonists, SLGT2 inhibitors, and insu-lin. HbA1c, hemoglobin HbA1c.

Glimepiride strongly enhances the glucose-lowering effect in triple oral antidiabetes therapy with sitagliptin and metformin for Japanese patients with type 2 diabetes mellitus.

After approval of sitagliptin and >750 mg of metformin in Japan, a triple oral antidiabetes drug (OAD) regimen including sulfonylurea, metformin, and sitagliptin was sometimes described. However, in the real world of clinical practice, the daily dose of sulfonylurea tended to be decreased according to the warning from the Japan Diabetes Society for avoiding hypoglycemia, instead of increasing the dose of metformin for maintaining hemoglobin A1c (HbA1c) levels with this regimen. This study examined the impact of either a small dose of glimepiride or a high dose of metformin on HbA1c in triple OAD therapy with sitagliptin in a 3-month, single-center, open-label, randomized controlled study. Fifty-six type 2 diabetes mellitus patients who had been treated with 50 mg of sitagliptin, ≥ 1,000 mg of metformin, and ≤ 1 mg of glimepiride with an HbA1c level of <7.4% during at least 3 months were enrolled in the study. The patients were randomly assigned to two treatment groups who either received a 50% reduced dose of metformin (n = 27) or discontinued glimepiride (n = 29), while sitagliptin administration continued in both groups. Twenty-six patients from the reduced metformin group and 27 patients from the discontinued glimepiride group completed the study. Significantly greater changes were observed in HbA1c and glycated albumin levels in patients who discontinued glimepiride than in patients with a 50% reduced metformin dose, during the 2-3-month period than in the 1-3-month period. Glimepiride is important for good glycemic control in triple OAD therapy with sitaglitpin and metformin. This regimen may be useful for those patients who do not achieve satisfactory glycemic control with dual combination therapy.


Stable angina in diabetics: this question is a nod to the BARI-2D study (NEJM 2009), which showed that medical management was not inferior to revascularization (in fact, the new guidelines reflect the trend that not all coronary stenosis should be systematically opened). Answer 1 is along these lines, although I miss statins, ACE inhibitors and antiplatelet agents, and I have too many vasodilators (nitrates are class IIb, if my memory serves me correctly). 2 is absurd: sitting down to avoid angina? That's like cutting down the forest to prevent fires. 3 to 5 are about revascularization: since it is a single vessel and not a proximal LAD, revascularization would have to be percutaneous, so we discard 3. Between 4 and 5, the fifth is more complete: not only would it be necessary to dilate, but also to implant a stent. So the doubt would be between 1 and 5. Applying the general rules of response in the MIR, if two options are similar except in one detail, the correct one is one of these, so we would mark 5 (and this is what would be done in any hospital nowadays: a suboccluded artery is dilated directly). On the other hand, and although 1 is incomplete, I suppose the author wanted to be clever and show that he has read the latest articles. Conclusion: I would mark 5... but I would not be surprised if it was 1.

Stable angina in diabetics: this question is a nod to the BARI-2D study (NEJM 2009), which showed that medical management was not inferior to revascularization (in fact, the new guidelines reflect the trend that not all coronary stenosis should be systematically opened). Answer 1 is along these lines, although I miss statins, ACE inhibitors and antiplatelet agents, and I have too many vasodilators (nitrates are class IIb, if my memory serves me correctly). 2 is absurd: sitting down to avoid angina? That's like cutting down the forest to prevent fires. 3 to 5 are about revascularization: since it is a single vessel and not a proximal LAD, revascularization would have to be percutaneous, so [HIDDEN]. Between 4 and 5, [HIDDEN]. So the doubt would be between 1 and 5. Applying the general rules of response in the MIR, if two options are similar except in one detail, [HIDDEN]. On the other hand, and although 1 is incomplete, I suppose the author wanted to be clever and show that he has read the latest articles. Conclusion: [HIDDEN]... but I would not be surprised if [HIDDEN].

In a 60-year-old diabetic patient with stable angina secondary to ischemic heart disease due to subtotal obstruction in the middle third of the anterior descending coronary artery, what treatment would you propose?

Medical with vasodilators and beta-blockers to avoid angina.

Expectorant with rigorous rest, since decreasing myocardial oxygen demand should decrease angina.

Surgical revascularization of the ischemic myocardium by means of a left mammary artery bypass distal to the lesion in the diseased coronary artery.

Dilatation of the coronary artery lesion by therapeutic catheterization.

Therapeutic catheterization to dilate the lesion of the diseased artery and implantation of a stent in the dilated area.

Coronary artery bypass surgery

Efficacy The 2004 ACC/AHA CABG guidelines state CABG is the preferred treatment for: Disease of the left main coronary artery (LMCA). Disease of all three coronary arteries (LAD, LCX and RCA). Diffuse disease not amenable to treatment with a percutaneous coronary intervention (PCI). The 2005 ACC/AHA guidelines further state that CABG is the preferred treatment with other high-risk patients such as those with severe ventricular dysfunction (i.e. low ejection fraction), or diabetes mellitus. Bypass surgery can provide relief of angina when the location of partial obstructions precludes improving blood flow with stents. There is no survival benefit with bypass surgery vs. medical therapy in stable angina patients. However, there is obvious benefit of CABG surgery when compared to medical therapy, as it prolongs survival not only in patients with 3-vessel disease but also with left main disease and 1- or 2- vessel disease with proximal LAD disease.

Coronary artery bypass surgery

Results compared to stent placement CABG or stent placement is indicated when medical management anti-angina medications, statins, antihypertensives, smoking cessation, and/or tight blood sugar control in diabetics do not satisfactorily relieve ischemic symptoms. Both PCI and CABG are more effective than medical management at relieving symptoms, (e.g. angina, dyspnea, fatigue). CABG is superior to PCI for most of the patients with multivessel CAD SYNTAX study found a 40% higher mortality in patient with 3-vessel coronary artery disease treated with PCI in comparison with CABG. The Surgery or Stent (SoS) trial was a randomized controlled trial that compared CABG to PCI with bare-metal stents. The SoS trial demonstrated CABG is superior to PCI in multivessel coronary disease.

Coronary artery disease

Stable angina In "stable" angina, chest pain with typical features occurring at predictable levels of exertion, various forms of cardiac stress tests may be used to induce both symptoms and detect changes by way of electrocardiography (using an ECG), echocardiography (using ultrasound of the heart) or scintigraphy (using uptake of radionuclide by the heart muscle). If part of the heart seems to receive an insufficient blood supply, coronary angiography may be used to identify stenosis of the coronary arteries and suitability for angioplasty or bypass surgery. Stable coronary artery disease (SCAD) is also often called stable ischemic heart disease (SIHD). A 2015 monograph explains that "Regardless of the nomenclature, stable angina is the chief manifestation of SIHD or SCAD." There are U.S. and European clinical practice guidelines for SIHD/SCAD. Acute coronary syndrome

Coronary artery disease

Coronary artery disease (CAD), also called coronary heart disease (CHD), ischemic heart disease (IHD), myocardial ischemia, or simply heart disease, involves the reduction of blood flow to the heart muscle due to build-up of plaque (atherosclerosis) in the arteries of the heart. It is the most common of the cardiovascular diseases. Types include stable angina, unstable angina, myocardial infarction, and sudden cardiac death. A common symptom is chest pain or discomfort which may travel into the shoulder, arm, back, neck, or jaw. Occasionally it may feel like heartburn. Usually symptoms occur with exercise or emotional stress, last less than a few minutes, and improve with rest. Shortness of breath may also occur and sometimes no symptoms are present. In many cases, the first sign is a heart attack. Other complications include heart failure or an abnormal heartbeat.

Revascularization

Applications For coronary artery disease (ischemic heart disease), coronary artery bypass surgery and percutaneous coronary intervention (coronary balloon angioplasty) are the two primary means of revascularization. When those cannot be done, transmyocardial revascularization or percutaneous myocardial revascularization, done with a laser, may be an option. Treatment for gangrene often requires revascularization, if possible. The surgery is also indicated to treat ischemic wounds (inadequate tissue perfusion) in some forms of chronic wounds, such as diabetic ulcers. References Vascular surgery

Transmyocardial revascularization

Transmyocardial laser revascularization (TMR) is a procedure used to treat inoperable heart disease in people with persistent angina that isn't relieved by any other revascularization method. Most people with coronary artery disease are treated with angioplasty and stenting or coronary bypass surgery and medications to improve blood flow to the heart muscle. The objective of each of these approaches is to increase blood flow through the coronary arteries to the heart. When these treatment options are exhausted, the patient is left with no viable surgical alternative other than, in limited cases, heart transplantation. Without a viable surgical alternative, the patient is generally managed with drug therapy, often with significant lifestyle limitations. TMR, or transmyocardial laser revascularization, is a newer treatment aimed at improving blood flow to areas of the heart that were not treated by angioplasty or surgery.

A preliminary experience report: Drug-eluting stents versus coronary artery bypass surgery in patients with a single lesion in the proximal left anterior descending artery suffering from diabetes mellitus and chronic stable angina.

Treatment of lesions located in the proximal segment of the left anterior descending artery (pLAD), either with coronary artery bypass grafting (CABG) or percutaneous coronary intervention, in patients with diabetes mellitus has been associated with an unfavourable outcome. The aim of the present study was to compare the long-term clinical outcome of drug-eluting stents (DES) vs. CABG with a left internal mammary artery (LIMA) graft in patients with a pLAD lesion who suffered from chronic stable angina and diabetes mellitus. We studied 77 consecutive patients suffering from chronic stable angina, diabetes mellitus, and with an isolated pLAD lesion. Thirty-nine patients underwent DES implantation and 38 LIMA grafting. Primary endpoints were the occurrence of major adverse cardiac events, defined as death, myocardial infarction, and target vessel revascularisation. Secondary endpoints included the length of stay in hospital, in-hospital complications, and the recurrence of chest pain. More in-hospital complications were observed in the CABG group than in the DES group. The mean duration of hospitalisation after CABG was 7.76 +/- 2.82 days vs. 1.17 +/- 1.15 days after DES. The mean follow-up period was 19.7 +/- 6.3 months for the DES group and 19.7 +/- 7.4 months for the surgical group. The incidence of major adverse cardiac events was similar in the two groups. There were two re-interventions in the DES group and none in the surgical group. Recurrent angina occurred in 2 patients in the DES group and 3 patients in the CABG group. The present study demonstrates that patients with diabetes mellitus, chronic stable angina, and single vessel disease in the pLAD have an excellent long-term outcome with both DES implantation and LIMA anastomosis. The surgical approach, however, was associated with more in-hospital complications and a longer hospitalisation.

Antianginal

Beta blockers Beta blockers are used in the prophylaxis of exertional angina by reducing the myocardial oxygen demand below the level that would provoke an angina attack. They are contraindicated in variant angina and can precipitate heart failure. They are also contraindicated in severe asthmatics due to bronchoconstriction, and should be used cautiously in diabetics as they can mask symptoms of hypoglycemia. Agents include either cardioselectives such as acebutolol or metoprolol, or non-cardioselectives such as oxprenolol or sotalol. Calcium channel blockers Calcium ion (Ca++) antagonists (Calcium channel blockers) are used in the treatment of chronic stable angina, and most effectively in the treatment of variant angina (directly preventing coronary artery vasospasm). They are not used in the treatment of unstable angina .

Percutaneous coronary intervention

The appropriateness of PCI use depends on many factors. PCI may be appropriate for patients with stable coronary artery disease if they meet certain criteria, such as having any coronary stenosis greater than 50 percent or having angina symptoms that are unresponsive to medical therapy. Although PCI may not provide any greater help in preventing death or myocardial infarction over oral medication for patients with stable coronary artery disease, it likely provides better relief of angina.

Coronary arteries

Clinical significance Narrowing of the arteries can be caused by a process known as atherosclerosis (most common), arteriosclerosis, or arteriolosclerosis. This occurs when plaques (made up of deposits of cholesterol and other substances) build up over time in the walls of the arteries. Coronary artery disease (CAD) or ischemic heart disease (IHD) are the terms used to describe narrowing of the coronary arteries. As the disease progresses, plaque buildup can partially block blood flow to the heart muscle. Without enough blood supply (ischemia), the heart is unable to work properly, especially under increased stress. Stable angina is chest pain on exertion that improves with rest. Unstable angina is chest pain that can occur at rest, feels more severe, and/or last longer than stable angina. It is caused by more severe narrowing of the arteries.

[Effect of Type 2 Diabetes on Results of Endovascular Treatment of Ischemic Heart Disease With Drug Covered Stents (Results of 1 Year Follow-up).].

Aim of the study was to determine the impact of sirolimus-eluting stents (SES) on clinical outcomes in patients with type 2 diabetes mellitus (DM) undergoing coronary revascularisation. The study enrolled 99 diabetic patients with de novo lesions in native coronary arteries. Medically treated DM was present in 61 patients (62%), 7 (7%) of whom required insulin. 53 patients received 78 SES and 46 patients received 57 bare metal stents. The differences in clinical outcomes between diabetic patients treated with SES and bare metal stents were assessed. Major adverse cardiac events (MACE) defined as death, myocardial infarction (MI), repeat revascularizations, and recurrences of angina were analyzed at 12-month follow-up. In the SES group the rate of recurrence of angina was 17%, the rate of coronary artery bypass surgery was 3,8%, the rate of repeat coronary angioplasty was 5,7%. In the bare metal stent group the rate of recurrence of angina was 37,8%, the rate of coronary artery bypass surgery was 2,2%, the rate of MI was 4,4%, the rate of repeat coronary angioplasty was 22,2%. Implantation of SES in patients with type 2 diabetes mellitus reduces recurrence of angina and major adverse cardiac events during first year after coronary angioplasty.

Coronary arteries

Reduced function of the coronary arteries can lead to decreased flow of oxygen and nutrients to the heart. Not only does this affect supply to the heart muscle itself, but it also can affect the ability of the heart to pump blood throughout the body. Therefore, any disorder or disease of the coronary arteries can have a serious impact on health, possibly leading to angina, a heart attack, and even death. Structure The coronary arteries are mainly composed of the left and right coronary arteries, both of which give off several branches as shown in the 'Coronary artery flow' figure. Aorta Left coronary artery (LCA) Left anterior descending artery Left circumflex artery Posterior descending artery Ramus or intermediate artery Right coronary artery (RCA) Right marginal artery Posterior descending artery

Coronary angioplasty for medically refractory unstable angina in patients with prior coronary bypass surgery.

Percutaneous transluminal coronary angioplasty (PTCA) has been applied with good results to selected patients with unstable angina and to selected patients who have had prior bypass surgery. The population with prior bypass and unstable angina has not been specifically evaluated. This report reviews the results of angioplasty of 45 vessels in 34 patients with medically refractory unstable angina and at least one prior bypass heart surgery. Of these 34 patients, 32 had rest angina; 14 had resting electrocardiographic changes, all 34 were on aspirin 325 mg QD, 31 were on a calcium blocker, 22 were on a beta blocker, 9 were on intravenous nitroglycerin, and 5 required intraaortic balloon counterpulsation for temporary stabilization. Angioplasty of a vein graft was attempted in 17 patients; the left internal mammary was attempted in 4 patients; 24 native coronary arteries in 15 patients were attempted; 3 of the native arteries were protected left main arteries. Of the LIMA angioplasties, 3 were successful; in the 1 unsuccessful case, the occluded anterior descending artery was opened. Of the 17 vein grafts, 16 were successful: 1 had an acute occlusive syndrome and went to surgery with a balloon pump and bail out catheter; his recovery was uneventful. Of the 24 native artery angioplasties, 22 were successful: one patient was technically unsuccessful in the only vessel attempted; he went to semiemergent surgery and recovered uneventfully. In the other, a right coronary lesion was successfully dilated, but an occluded anterior descending artery was not opened. There were no deaths or in-hospital myocardial infarctions.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary ischemia

Other medications may be used to reduce the symptoms of coronary ischemia, particularly angina. Long and short acting nitrates are one option for reducing anginal pain. Nitrates reduce the symptoms of angina by dilating blood vessels around the heart, which increases oxygen-rich blood supply to the muscle cells of the heart. Veins are also dilated, which reduces return of blood to the heart, easing strain on the heart muscle. Short-acting nitrates can be taken upon the onset of symptoms and should provide relief within minutes. Nitroglycerin is the most common short-acting nitrate and it is applied under the tongue. Long acting nitrates are taken 2-3 times per day and can be used to prevent angina. Beta-blockers may also be used to reduce the incidence of chronic angina. Beta-blockers prevent episodes of angina by reducing heart rate and reducing the strength of contraction of the heart, which lowers oxygen demand in the heart.

Angina

In patients in whom such noninvasive testing is diagnostic, a coronary angiogram is typically performed to identify the nature of the coronary lesion, and whether this would be a candidate for angioplasty, coronary artery bypass graft (CABG), treatment only with medication, or other treatments. In hospitalized patients with unstable angina (or the newer term of "high-risk acute coronary syndromes"), those with resting ischaemic ECG changes or those with raised cardiac enzymes such as troponin may undergo coronary angiography directly. Treatment

Coronary artery bypass surgery

A study comparing the outcomes of all patients in New York state treated with CABG or percutaneous coronary intervention (PCI) demonstrated CABG was superior to PCI with DES in multivessel (more than one diseased artery) coronary artery disease (CAD). Patients treated with CABG had lower rates of death and of death or myocardial infarction than treatment with a coronary stent. Patients undergoing CABG also had lower rates of repeat revascularization. The New York State registry included all patients undergoing revascularization for coronary artery disease, but was not a randomized trial, and so may have reflected other factors besides the method of coronary revascularization. A meta-analysis with over 6000 patients showed that coronary artery bypass was associated with lower risk for major adverse cardiac events compared to drug-eluting stenting. However, patients had a higher risk of stroke events.

Angina

Women with myocardial ischemia often have either no or atypical symptoms, such as palpitations, anxiety, weakness, and fatigue. Additionally, many women with angina are found to have cardiac ischemia, yet no evidence of obstructive coronary artery disease on cardiac catheterization. Evidence is accumulating that nearly half of women with myocardial ischemia suffer from coronary microvascular disease, a condition often called microvascular angina (MVA). Small intramyocardial arterioles constrict in MVA causing ischemic pain that is less predictable than with typical epicardial coronary artery disease (CAD). The pathophysiology is complex and still being elucidated, but there is strong evidence that endothelial dysfunction, decreased endogenous vasodilators, inflammation, changes in adipokines, and platelet activation are contributing factors. The diagnosis of MVA may require catheterization during which there is an assessment of the microcirculatory response to adenosine or

[Statistical analysis of decision making in the treatment in two-vessel coronary artery disease].

The objective of this paper was to analyze the choice of treatment in two-vessel coronary artery disease and to evaluate the effectiveness of the chosen treatment. The data of sixty-five patients with two-vessel coronary artery disease was analyzed. Two-vessel coronary artery disease was recognized when critical stenoses were present in two arteries with a diameter no less than 2 mm across. Patients who had a CABG were excluded. Patients were divided into three groups according to their treatment: those treated with CABG (29 patients), those treated with coronary angioplasty (20 patients), and those treated conservatively (16 patients). The mean follow-up was 29.3 months (12-48 mo). There were two groups of data collected. The first group consisted of data which might have influenced the decision-making and state of the patients after they had been introduced to the selected treatment. The second group consisted of data necessary to evaluate the state of the patients during the follow-up period. The statistical analysis was divided into three stages. In the first stage, clinical data connected to the selected treatments was studied. In the second, the effects of the chosen treatment were examined. During the third stage of analysis, variables which influenced the effectiveness of the specific treatment were evaluated. Decision-making in patients with two-vessel coronary artery disease depended on the co-existence of hypertension, diabetes, lower-limb ischemia and earlier-performed coronary angioplasty. The only statistically important angiographic feature was the condition of the proximal LAD. Objective improvements in the states of patients (evaluated by exercise tests) were frequently connected to CABG treatment. Subjective improvements in the states of patients were more often connected to conservative treatment. Elevated cholesterol levels were connected to the progression of the disease both in those treated conservatively and interventionally.

[Myocardial revascularization of patients with diffuse coronary artery disease].

Off-pump coronary artery bypass grafting (off-pump CABG) after off-pump coronary endarterectomy (CE) for myocardial revascularization is a way to rescue the patients with diffuse coronary artery disease (CAD). This study retrospectively analyzed its clinical outcomes and experiences, and explored the safety and effectiveness. From October 2003 to December 2008, 177 diffuse CAD patients with 229 vascular lesions received off-pump CABG plus CE. Incision was made at the hardest part of coronary artery and ≥ 2 cm from the distal intervention site. Then bypass graft was performed by internal mammary artery or saphenous vein. The intra-operative blood tests showed that 215 (93.9%) bridges were satisfied with (27 ± 12) ml/min blood flow while 14 bridges were dissatisfied. The blood flow was (7 ± 4) ml/min. Six (3.4%) cases suffered peri-operative myocardial infarction. Among them, 3 patients had no significant cardiac hemodynamic changes. Three suffered a low cardiac output and improved by intra-aortic balloon counter pulsation support. And they were then discharged after treatment. After 3 - 40 months, 98 patients underwent coronary angiography to measure the graft latency. And the blood flow was excellent. Off-pump CABG plus CE for diffuse coronary artery disease is both feasible and safe. And it is an effective treatment with a high degree of vascularization.

Hybrid cardiac surgery

Clinical applications Hybrid revascularization approach for coronary artery disease Surgical bypass grafting and percutaneous coronary artery revascularization are traditionally considered isolated options. A simultaneous hybrid approach may allow an opportunity to match the best strategy for a particular anatomic lesion. Thus hybrid coronary revascularization and MIDCAB (minimally invasive direct coronary artery bypass surgery) have been developed. Revascularization of the left anterior descending artery with the left internal mammary artery is by far the best treatment option in terms of long-term results. Integrating this therapy with percutaneous coronary angioplasty (hybrid procedure) offers multi-vessel revascularization through a mini-thoracotomy. Particularly in high risk patients, morbidity and mortality decreases in comparison to conventional surgery. Completion angiography

[Ischemia--reliable results of therapy, operation and angioplasty--in coronary disease].

Randomized studies have shown that coronary bypass-surgery is effective in prolonging survival and reducing symptoms in various groups of patients with coronary artery disease, when compared with medical therapy alone. This effect is most pronounced and stable in patients who received an internal-mammary-artery graft. Therefore internal-mammary-artery grafting for lesions of the left anterior descending coronary artery is preferable whenever indicated and technically feasible. While percutaneous transluminal coronary angioplasty is effective in improving symptoms of angina pectoris, beneficial effects on survival have not yet been shown. In randomized trials of PTCA versus bypass-surgery acute results were comparable. During follow-up significantly less re-interventions and more angina-free patients were seen in the bypass-groups, indicating a more stable result after bypass surgery. In older patients with a higher mortality and rate of cerebral vascular events during surgery, a palliative PTCA of the culprit lesion may be superior to the bypass-operation. For the often used "unproven" indications for PTCA (silent ischemia, infarct-related artery in asymptomatic patients, isolated proximal LAD-stenosis, acute myocardial infarction, cardiogenic shock) larger randomized trials should be awaited to prove the effectiveness of PTCA in these settings.

Coronary Artery Disease -- Treatment / Management -- Stable Ischemic Heart Disease

Every patient should get guideline-directed medical therapy (GDMT) which includes low dose aspirin, beta-blocker, as-needed nitroglycerin, and moderate to high-intensity statin. If symptoms are not controlled with this, beta-blocker therapy should be titrated up to heart rates 55-60, and the addition of calcium channel blocker and long-acting nitrates should be considered. [10] Ranolazine could also be added to relieve refractory anginal symptoms. If maximal GDMT has failed to relive angina, cardiac catheterization should be done to visualize the coronary anatomy and a decision should be made for percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) based on the patient profile. [11]

List of MeSH codes (C14)

– ischemia – brain ischemia – colitis, ischemic – compartment syndromes – anterior compartment syndrome – infarction – brain infarction – brain stem infarctions – lateral medullary syndrome – cerebral infarction – dementia, multi-infarct – infarction, anterior cerebral artery – infarction, middle cerebral artery – infarction, posterior cerebral artery – myocardial infarction – myocardial stunning – shock, cardiogenic – pulmonary embolism – splenic infarction – myocardial ischemia – coronary disease – angina pectoris – angina pectoris, variant – angina, unstable – microvascular angina – coronary aneurysm – Coronary Arteriosclerosis – coronary stenosis – coronary restenosis – coronary thrombosis – coronary vasospasm – angina pectoris, variant – myocardial infarction – myocardial stunning – shock, cardiogenic – myocardial stunning – optic neuropathy, ischemic – reperfusion injury – myocardial reperfusion injury

[Indications for coronary dilatation and bypass surgery].

Coronary artery disease is the dominant disorder in industrialized countries. It can be treated by drugs, coronary angioplasty, or bypass surgery. Angioplasty has become the most frequent mode of active therapy. Local variations in the use of treatment modalities can be explained mainly by early detection of coronary artery disease yielding more candidates for angioplasty. All indications should be based on a combination of symptoms, objective signs of ischemia (e.g., stress test) and angiographic correlates. Coronary angioplasty is limited to the less complex cases such as single vessel disease (except for diffuse disease, old total occlusions), double vessel disease with up to 3 discrete lesions or lesions in secondary vessels, and, exceptionally, triple vessel disease of the appropriate kind (usually in 2 sessions). These limitations arise from the drawbacks of the method, i.e., acute occlusion (about 7%), recurrence (about 30%), and technical failures (about 5%). For acute myocardial infarction, direct coronary angioplasty is probably the method of choice, provided it can be performed within 30 minutes after diagnosis. For unstable angina, the results are inferior to those obtained with stable symptomatology; compared with the spontaneous prognosis, they remain nonetheless beneficial. The same holds true for angioplasty in elderly patients, where the reduced chances of success must be viewed in light of a typically very severe clinical picture. Angioplasty is often a blessing for young patients. It allows immediate resumption of a normal life and is easily repeatable over the years. Indications for coronary bypass surgery should not be deduced from the randomized studies of the seventies. They concentrated on survival, and surgical methods have been refined since.(ABSTRACT TRUNCATED AT 250 WORDS)

[Results of coronary revascularization in occluded coronary arteries].

In a total of 82 patients (age 37-71 years) with an occluded left anterior descending artery (LAD) the results of coronary revascularization were evaluated 7 months postoperatively on average. In all patients the indications for revascularization was given by clinical symptoms (angina pectoris) or by prognostic reasons. In patients with multivessel disease. In patients with anterior wall infarction viable myocardium was proven by thallium-scintigram at rest and during exercise. 29 patients were evaluated by coronary angiography postoperatively, in 19 patients the angiograms of the left ventricle could be assessed quantitatively. Total patency rate was 76%, for the LAD 69%, for the circumflex artery 73% and for the right coronary artery 83%. The relatively low patency rate for the LAD was caused by an increased collateral flow to the occluded LAD and therefore by a significantly lower bypass flowrate measured during surgery. Angina pectoris improved markedly, 55% of patients had angina pectoris class III or IV versus 10% postoperatively. These changes were observed in all patients irrespectively of patency rate or occluded grafts to the LAD. Left ventricular volumes and ejection fraction did not change on average after revascularization. Only end-diastolic volume increased significantly in patients with an occluded graft to the LAD. There was a tendency of the end-systolic volume to decrease postoperatively in patients with complete revascularization or at least an open graft to the LAD. The results show a similar clinical improvement in these patients with occluded LAD as shown after "usual" revascularization in other patients. Preoperative coronary angiograms are helpful in judging the postoperative outcome of grafts to the occluded LAD.

Angina

The other class of medication that can be used to treat angina are the organic nitrates. Organic nitrates are used extensively to treat angina. They improve coronary blood flow of the coronary arteries (arteries which supply blood to the heart muscle) by reversing and preventing vasospasm, which increases the blood flow to the heart, improving perfusion and oxygen delivery to the heart associated with the pain of angina. These drugs also reduce systemic vascular resistance, of both veins and arteries but the veins to a greater extent. The decrease in the resistance of the arteries and veins decreases the myocardial oxygen demand, which also reduces myocardial oxygen demand. Nitroglycerin is a potent vasodilator that decreases myocardial oxygen demand by decreasing the heart's workload. Nitroglycerin should not be given if certain inhibitors such as sildenafil, tadalafil, or vardenafil have been taken within the previous 12 hours as the combination of the two could cause a serious

[Coronary occlusion immediately following a successful coronary angioplasty. Treatment by repeat angioplasty].

The authors report the case of a 52 year old patient with a significant stenosis of the medial portion of the left anterior descending artery (LAD) with excellent left ventricular function. Transluminal coronary angioplasty (TCA) was indicated following a positive exercise stress test. This was initially performed successfully. Fifteen minutes after the end of the procedure, a total obstruction occurred at the site of dilatation immediately eliciting significant precordial chest pain and massive elevation of the ST segment. Isosorbide dinitrate (ISDN) at a dose of 2 mg was injected into the artery 3 times without success as was an attempt to pass through the obstruction with a guide wire. Another TCA was then attempted without administration of the thrombolytic agent. The dilating catheter passed easily by the obstruction permitting several dilatations which restored rapid coronary artery flow, relieved completely the chest pain, and normalized electrocardiographic abnormalities. This procedure represents a new therapeutic approach to obstruction, an often unpredictable and serious complication of coronary angioplasty in the absence of collateral circulation, thereby preventing the development of a myocardial infarction and an emergency aortocoronary bypass operation.

[Early clinical results of balloon coronary angioplasty in patients with ischemic heart disease and three impaired coronary vessels].

To study a short-term clinical effect of balloon coronary angioplasty (BCA) in patients with affection of three coronary arteries regarding an anginal form and completeness of myocardial revascularization. The study included 80 patients with coronary heart disease (CHD) having three affected major coronary arteries after BCA among them 48 patients with stable and 32 patients with unstable angina. The procedures were made using "Polydiagnost C" angiographic complex (Philips, Holland). Overall clinical efficacy of BCA in affection of three coronary arteries was 88.75% (in 71 of 80 patients), no response was observed in 9 of 80 patients (11.25%). The response to BCA was independent of the anginal form. In stable angina there were no differences in clinical efficacy in complete and incomplete functionally-adequate anatomic BCA (91 and 89.6%, respectively). In incomplete anatomic revascularization clinical effect was less (62.5%). In unstable angina a clinical effect of BCA did not depend on the degree of myocardial revascularization. Stenting raised clinical response to BCA in all the patients. The findings demonstrate high clinical efficacy of BCA in affection of three coronary arteries irrespective of an angina form. Incomplete anatomic revascularization in stable effort angina is less effective but can be used if other operations are impossible. If definition of the symptom-causing artery is possible, the intervention should be limited to BCA of this artery to decide on dilation of other arteries later.

Angina

Angina pectoris occurs as a result of coronary blood flow insufficiency in the face of increased oxygen demand. The principal goal in the prevention and relief of angina is to limit the oxygen requirement of the heart so it can meet the inaqedate oxygen supply derived through the blood supplied from the stenosed or constricted arteries. The main goals of treatment in angina pectoris are relief of symptoms, slowing progression of the disease, and reduction of future events, especially heart attacks and death. Beta blockers (e.g., carvedilol, metoprolol, propranolol) have a large body of evidence in morbidity and mortality benefits (fewer symptoms, less disability and longer life) and short-acting nitroglycerin medications have been used since 1879 for symptomatic relief of angina. There are differing course of treatments for the patient depending on the type of angina the patient has. However, this second can provide a brief overview of the types of medications provided for angina and

Percutaneous coronary intervention

Primary PCI is the urgent use of PCI in people with acute heart attack, especially where there is evidence of heart damage on the electrocardiogram. PCI is also used in people after other forms of myocardial infarction or unstable angina where there is a high risk of further events. Finally, PCI may be used in people with stable angina pectoris, particularly if the symptoms are difficult to control with medication. PCI is an alternative to coronary artery bypass grafting (CABG, often referred to as "bypass surgery"), which bypasses stenotic arteries by grafting vessels from elsewhere in the body. Under certain circumstances such as extensive blockages, background of diabetes, CABG may be superior. Coronary angioplasty was first introduced in 1977 by Andreas Gruentzig in Switzerland. Medical uses

Angioplasty

The word is composed of the combining forms of the Greek words ἀνγεῖον "vessel" or "cavity" (of the human body) and πλάσσω "form" or "mould". Uses and indications Coronary angioplasty A coronary angioplasty is a therapeutic procedure to treat the stenotic (narrowed) coronary arteries of the heart found in coronary heart disease. These stenotic segments of the coronary arteries arise due to the buildup of cholesterol-laden plaques that form in a condition known as atherosclerosis. A percutaneous coronary intervention (PCI), or coronary angioplasty with stenting, is a non-surgical procedure used to improve the blood flow to the heart. Coronary Angioplasty is indicated for coronary artery disease such as unstable angina, NSTEMI, STEMI and spontaneous coronary artery perforation. PCI for stable coronary disease has been shown to significantly relieve symptoms such as angina, or chest pain, thereby improving functional limitations and quality of life. Peripheral angioplasty

[Clinical and angiographic expression of myocardial ischemia in stable angina as a function of its coronary reserve].

We have studied the distribution of the coronary reserve, evaluated by serial effort tests, in patients with proved coronaropathy, determining the correlation between clinic (effort and mixed angina) and coronary reserve (fixed and variable), assessing angiographic findings in function to that reserve. We took 120 patients with stable angina to whom 2 effort tests were performed, basal and after vasodilator drugs. It was considered variable reserve if in the second test the S-T descend improved greater than or equal to 1 mm for a similar of greater double product and fixed when it didn't improve. In all patients coronarography was performed. Seventy two patients (60%) showed fixed reserve, 58 with effort angina (80%) and 14 (20%) with mixed. Forty eight showed variable reserve, 40 (80%) with mixed angina and 8 (17%) with effort. The group with fixed reserve had a greater S-T max. descent (2.9 +/- 0.9 vs 2.2 +/- 0.4) (p less than 0.001), a lower double product max. (221 +/- 44 vs 284 +/- 37) (p less than 0.001) and a lower maximal oxygen consumption (MVO2 7 +/- 2 vs 11 +/- 2) (p less than 0.001) than the variable reserve group. Considering the angiography, the fixed reserve group had more number of vessels affected (1.9 +/- 0.7 vs 1.4 +/- 0.5) (p less than 0.01), a higher angiographic score (4.88 +/- 2.4 vs 2.2 +/- 1.2) (p less than 0.001), a lower ejection fraction (59 +/- 8.5 vs 65 +/- 7.5) (p less than 0.001), more multivessel and descending anterior artery lesion than the variable reserve group.(ABSTRACT TRUNCATED AT 250 WORDS)