Bicarbonate is indicated at pH < 7.

Easy question since the treatment of diabetic ketoacidosis is a very repeated topic in the MIR. Bicarbonate is indicated at pH < 7.

A type 1 diabetic who comes to the emergency room for dyspnea and general malaise. The blood test showed blood glucose 450 mg/dl, Na 142 mEq/l, K 4 mEq/l, pH 7.15, bicarbonate 12 mmol/l. Which treatment would NOT be indicated?

Serum glucose 5% iv when blood glucose is less than 250 mg/dl.

Potassium chloride 100 mEq / day diluted in sera.

Sodium bicarbonate 1M 100 cc iv in 30 minutes.

[Opportunities to improve hospital emergency care of patients with diabetic ketoacidosis].

To identify opportunities to improve the care of adult patients with diabetic ketoacidosis in the emergency room. Retrospective observational study of records for 2010 to 2013. Searching for International Classification of Diseases discharge codes 250.1–250.3 we identified patients who met the following 3 criteria: ketonuria of 100 mg/dL or more, diagnosed diabetes or glucose concentration of 250 mg/dL or more, and venous blood pH below 7.30 (or venous bicarbonate concentration less than 18 mEq/L). We reviewed the cases to extract patient and clinical characteristics and time from triage until diagnosis and start of treatment. The findings were compared with recommendations in clinical practice guidelines. We identified 49 episodes of diabetic ketoacidosis (4 mild, 32 moderate, and 13 severe) in 43 patients. The median delay between triage until the first blood test results were available was 142 minutes (range, 59-597 minutes). In 50% of the cases fluid therapy was delayed beyond the time recommended in clinical practice guidelines. Intravenous insulin was also delayed (in 66%) and insuficient intravenous potassium was given in 65%. Sodium bicarbonate was overused (in 50%). Half the patients developed hypokalemia in the hospital. Diagnosis and initiation of treatment were often delayed for patients with diabetic ketoacidosis in our emergency department.

A prospective study of the "two-bag system'' in diabetic ketoacidosis management.

The "two-bag'' system, an adaptation of the euglycemic clamp technique, consists of simultaneous administration of 2 intravenous (IV) fluid bags of differing dextrose concentrations. Individualized therapy is dictated by adjustment of the infusion rate of each bag. We sought to assess the benefits of the two-bag system in the initial acute emergency department management of children in diabetic ketoacidosis (DKA). Thirty-three children presenting to an urban pediatric emergency department in DKA were randomized into 2 groups: patients managed with the two-bag system and patients managed with the traditional "one-bag'' system. Other aspects of the management were standardized. Outcome measures included rate of decline in serum glucose, rate of bicarbonate correction, time on IV insulin therapy, and response time for IV fluid changes. Study period was defined as time on IV insulin therapy. There were no differences between the 2 groups in demographic parameters, initial baseline metabolic parameters, or total time on IV insulin therapy. There were no differences between the groups in average rates of serum glucose decline: two-bag 33.1 mg/dL/hr (s.e. 5.57, 95% CI 22.2, 44), one-bag 30.2 mg/dL/hr (s.e. 5.72, 95% CI 19, 41.4); average rate of serum bicarbonate correction: two-bag 1.19 mEq/L/hr, one-bag 1.27 mEq/L/hr; or the average number of IV fluid bags used: two-bag 4.1 bags, one-bag 3.2 bags. However, there was a difference between the groups in regard to elapsed total time to make changes in the IV fluids: two-bag 1 minute, one-bag 42 minutes, (p < 0.001). The "two-bag'' system enables a faster response time in making IV fluid therapy changes. This efficiency makes this system ideal for use in the emergency department.

Crush syndrome

Intravenous hydration of up to 1.5 L/h should continue to prevent hypotension. A urinary output of at least 300 mL/h should be maintained with IV fluids and mannitol, and hemodialysis considered if an increase in urine is not achieved. Use intravenous sodium bicarbonate to keep the urine pH at 6.5 or greater, to prevent myoglobin and uric acid deposition in kidneys. To prevent hyperkalemia/hypocalcemia, consider the following adult doses: calcium gluconate 10% 10 mL or calcium chloride 10% 5 mL IV over 2 minutes sodium bicarbonate 1 meq/kg IV slow push regular insulin 5–10 U 50% glucose 1–2 ampules IV bolus kayexalate 25–50 g with sorbitol 20% 100 mL by mouth or rectum. Even so, abnormal heart rhythms may develop; electrocardiographic monitoring is advised, and specific treatment begun promptly. References External links Life or Limb: What happens when your leg gets trapped under a building? Injuries Early complications of trauma Nephrology Syndromes

Hyperosmolar hyperglycemic state

Management Intravenous fluids Treatment of HHS begins with reestablishing tissue perfusion using intravenous fluids. People with HHS can be dehydrated by 8 to 12 liters. Attempts to correct this usually take place over 24 hours with initial rates of normal saline often in the range of 1 L/h for the first few hours or until the condition stabilizes. Electrolyte replacement Potassium replacement is often required as the metabolic problems are corrected. It is generally replaced at a rate 10 mEq per hour as long as there is adequate urinary output. Insulin Insulin is given to reduce blood glucose concentration; however, as it also causes the movement of potassium into cells, serum potassium levels must be sufficiently high or dangerously low blood potassium levels may result. Once potassium levels have been verified to be greater than 3.3 mEq/l, then an insulin infusion of 0.1 units/kg/hr is started. The goal for resolution is a blood glucose of less than 200 mg/dL. References

InternalMed_Harrison

3. Assess: Serum electrolytes (K+, Na+, Mg2+, Cl−, bicarbonate, phosphate) Acid-base status—pH, HCO3−, PCO2, β-hydroxybutyrate Renal function (creatinine, urine output) 4. Replace fluids: 2–3 L of 0.9% saline over first 1–3 h (10–20 mL/kg per hour); subsequently, 0.45% saline at 250–500 mL/h; change to 5% glucose and 0.45% saline at 150–250 mL/h when plasma glucose reaches 250 mg/dL (13.9 mmol/L). 5. Administer short-acting insulin: IV (0.1 units/kg), then 0.1 units/kg per hour by continuous IV infusion; increase twoto threefold if no response by 2–4 h. If the initial serum potassium is <3.3 mmol/L (3.3 meq/L), do not administer insulin until the potassium is corrected. 6. Assess patient: What precipitated the episode (noncompliance, infection, trauma, pregnancy, infarction, cocaine)? Initiate appropriate workup for precipitating event (cultures, CXR, ECG). 7.

Glucose tolerance test

For gestational diabetes, the American College of Obstetricians and Gynecologists (ACOG) recommends a two-step procedure, wherein the first step is a 50 g glucose dose. If after 1 hour the blood glucose level is more than 7.8 mmol/L (140 mg/dL), it is followed by a 100 g glucose dose. The diagnosis of gestational diabetes is then defined by a blood glucose level meeting or exceeding the cutoff values on at least two intervals, with cutoffs as follows: Before glucose intake (fasting): 5.3 mmol/L (95 mg/dL) 1 hour after drinking the glucose solution: 10.0 mmol/L (180 mg/dL) 2 hours: 8.6 mmol/L (155 mg/dL) 3 hours: 7.8 mmol/L (140 mg/dL)

Hyperosmolar hyperglycemic state

Diagnosis Criteria According to the American Diabetes Association, diagnostic features include: Plasma glucose level >30 mmol/L (>600 mg/dL) Serum osmolality >320 mOsm/kg Profound dehydration, up to an average of 9L (and therefore substantial thirst (polydipsia)) Serum pH >7.30 Bicarbonate >15 mEq/L Small ketonuria (~+ on dipstick) and absent-to-low ketonemia (<3 mmol/L) Some alteration in consciousness BUN > 30 mg/dL (increased) Creatinine > 1.5 mg/dL (increased) Imaging Cranial imaging is not used for diagnosis of this condition. However, if MRI is performed, it may show cortical restricted diffusion with unusual characteristics of reversible T2 hypointensity in the subcortical white matter.

Combined effect of bicarbonate and insulin with glucose in acute therapy of hyperkalemia in end-stage renal disease patients.

This study was performed to evaluate the efficacy of various treatment modalities for hyperkalemia in 8 end-stage renal disease (ESRD) patients. Simultaneous administration of sodium bicarbonate and insulin with glucose was compared with infusion of either bicarbonate alone or insulin and glucose. Plasma potassium was measured at the baseline and after 60 min of infusion with each regimen. Infusion of 8.4% solution of sodium bicarbonate at 2 mEq/min for 60 min induced a significant rise in blood bicarbonate from 21.7 +/- 2.1 to 26.3 +/- 1.7 mEq/l (p < 0.01), but failed to lower plasma potassium (6.4 +/- 0.1 vs. 6.3 +/- 0.2 mEq/l, before and after). Intravenous infusion of insulin and glucose (5 mU/kg/min for 60 min) significantly lowered plasma potassium from 6.3 +/- 0.1 to 5.7 +/- 0.1 mEq/l (p < 0.01). The combined infusion of bicarbonate and insulin with glucose showed the greatest decline in plasma potassium, from 6.2 +/- 0.2 to 5.2 +/- 0.1 mEq/l (p < 0.01). With the combined regimen, the increases in plasma bicarbonate (22.3 +/- 1.7 to 25.8 +/- 1.9 mEq/l, p < 0.05) and blood pH (7.36 +/- 0.02 to 7.42 +/- 0.02, p < 0.01) were significant, but somewhat less than those with bicarbonate administration alone. Plasma insulin levels before treatment were similar in all treatment regimens, and increased markedly following the infusion of insulin with glucose, either with or without sodium bicarbonate (9 +/- 1.5 vs. 10 +/- 10 microU/ml before insulin, and 196 +/- 18.0 vs. 201 +/- 26.4 microU/ml after insulin). Plasma epinephrine, norepinephrine, osmolality and plasma aldosterone before and after treatment did not show any significant differences among the 3 different regimens. In conclusion, the ineffectiveness of sodium bicarbonate alone and its synergistic effect with insulin and glucose in acute therapy of hyperkalemia in ESRD patients suggest that mild metabolic acidosis, which is common in patients on maintenance hemodialysis, may contribute to tissue insensitivity to the action of insulin on transcellular potassium shift.

Glucose test

Reference ranges Fasting blood sugar A level below 5.6 mmol/l (100 mg/dl) 10–16 hours without eating is normal. 5.6–6 mmol/l (100–109 mg/dl) may indicate prediabetes and oral glucose tolerance test (OGTT) should be done for high-risk individuals (old people, those with high blood pressure etc.). 6.1–6.9 mmol/l (110–125 mg/dl) means OGTT should be done even if other indicators of diabetes are not present. 7 mmol/l (126 mg/dl) and above indicates diabetes and the fasting test should be repeated. Glucose tolerance test Postprandial glucose test Random glucose test See also Hyperglycemia Hypoglycemia References Blood tests

Surgery_Schwartz

removal Kayexalate Oral administration is 15–30 g in 50–100 mL of 20% sorbitol Rectal administration is 50 g in 200 mL of 20% sorbitol DialysisShift potassium Glucose 1 ampule of D50 and regular insulin 5–10 units IV Bicarbonate 1 ampule IVCounteract cardiac effects Calcium gluconate 5–10 mL of 10% solutionD50 = 50% dextrose.Brunicardi_Ch03_p0083-p0102.indd 9508/12/18 10:07 AM 96BASIC CONSIDERATIONSPART ITable 3-15Electrolyte replacement therapy protocolPotassiumSerum potassium level <4.0 mEq/L: Asymptomatic, tolerating enteral nutrition: KCl 40 mEq per enteral access × 1 dose Asymptomatic, not tolerating enteral nutrition: KCl 20 mEq IV q2h × 2 doses Symptomatic: KCl 20 mEq IV q1h × 4 doses Recheck potassium level 2 h after end of infusion; if <3.5 mEq/L and asymptomatic, replace as per above protocolMagnesiumMagnesium level 1.0–1.8 mEq/L: Magnesium sulfate 0.5 mEq/kg in normal saline 250 mL infused IV over 24 h × 3 d Recheck magnesium level in 3 dMagnesium level <1.0

Euglycemic Diabetic Ketoacidosis -- Treatment / Management

Initial management should be directed toward fluid resuscitation, as patients usually present as profoundly dehydrated. Begin with the administration of isotonic saline or lactated ringers solution. The American Diabetes Association (ADA) recommends 1 to 1.5 L/hr isotonic fluids during the first 1 to 2 hours. Continuous insulin infusion should follow fluid replacement, contingent on serum potassium levels greater than 3.3 mEq/L, starting at a rate of 0.05 to 0.1 U/kg/hr. In contrast to DKA management, since serum glucose in EDKA is less than 250 mg/dL, dextrose 5% should initially be added to the fluids to avoid hypoglycemia and hasten clearance of ketosis. [34] Consider increasing the amount of dextrose to 10% if ketoacidosis persists on D5%. [27] [35] [27]

Insulinoma

During the test, the patient may have calorie-free and caffeine-free liquids. Capillary blood glucose is measured every 4 hours using a reflectance meter, until values < 60 mg/dL (3.3 mmol/L) are obtained. Then, the frequency of blood glucose measurement is increased to every hour until values are < 49 mg/dL (2.7 mmol/L). At that point, or when the patient has symptoms of hypoglycemia, a blood test is drawn for serum glucose, insulin, proinsulin, and C-peptide levels. The fast is then stopped at that point, and the hypoglycemia is treated with intravenous dextrose or carbohydrate-containing food or drink.

Prediabetes

Diagnosis Prediabetes can be diagnosed with three different types of blood tests: Fasting blood sugar (glucose) level of: 110 to 125 mg/dL (6.1 mmol/L to 6.9 mmol/L) – WHO criteria 100 to 125 mg/dL (5.6 mmol/L to 6.9 mmol/L) – ADA criteria Glucose tolerance test: blood sugar level of 140 to 199 mg/dL (7.8 to 11.0 mM) 2 hours after ingesting a standardized 75 gram glucose solution Glycated hemoglobin (HbA1c) between 5.7 and 6.4 percent, ie 38.9 and 46.4 mmol/mol Levels above these limits would justify a diagnosis for diabetes. Impaired fasting glucose

Bicarbonate therapy in severe diabetic ketoacidosis. A double blind, randomized, placebo controlled trial.

Intravenous sodium bicarbonate has been used for a long time in the treatment of diabetic ketoacidosis. However, there are no clinical studies showing its effectiveness in improving arterial pH in this condition. We therefore designed this study to investigate if bicarbonate therapy improves the rate of increase of arterial pH and to find out its effects on the recovery rate of the other metabolic abnormalities. Twenty patients with severe diabetic ketoacidosis (pH less than 7.15) entered a double-blind, randomized, placebo controlled trial: nine were included in the bicarbonate group and eleven in the placebo group. All patients were studied during the first 24 hours of treatment. Their management was similar, except for the use of sodium bicarbonate in one group and 0.9% saline solution in the placebo group. Heart rate, respiratory rate, arterial pressure, mental status, blood gases, blood glucose, sodium, potassium, and urea were assessed at the beginning of treatment, and then at 2, 6, 12 and 24 hours. No clinical or metabolic differences were found between groups. Two hours after therapy was begun, the arterial pH rose in the bicarbonate group from 7.05 +/- 0.08 to 7.24 +/- 0.04, while it only rose from 7.04 +/- 0.08 to 7.11 +/- 0.09 in the placebo group (p less than 0.02). Simultaneously, arterial bicarbonate increased from 2.87 +/- 1.2 to 6.1 +/- 1.5 mEq/L in the bicarbonate group and from 2.55 +/- 0.81 to 3.6 +/- 2 mEq/L in the placebo group (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Type 2 diabetes

fasting plasma glucose ≥ 7.0 mmol/l (126 mg/dl) or with a glucose tolerance test, two hours after the oral dose a plasma glucose ≥ 11.1 mmol/l (200 mg/dl) A random blood sugar of greater than 11.1 mmol/l (200 mg/dl) in association with typical symptoms or a glycated hemoglobin (HbA1c) of ≥ 48 mmol/mol (≥ 6.5 DCCT %) is another method of diagnosing diabetes. In 2009 an International Expert Committee that included representatives of the American Diabetes Association (ADA), the International Diabetes Federation (IDF), and the European Association for the Study of Diabetes (EASD) recommended that a threshold of ≥ 48 mmol/mol (≥ 6.5 DCCT %) should be used to diagnose diabetes. This recommendation was adopted by the American Diabetes Association in 2010. Positive tests should be repeated unless the person presents with typical symptoms and blood sugars >11.1 mmol/l (>200 mg/dl).

Hyperglycemia

Scientific journals are moving towards using mmol/l; some journals now use mmol/l as the primary unit but quote mg/dl in parentheses. Glucose levels vary before and after meals, and at various times of day; the definition of "normal" varies among medical professionals. In general, the normal range for most people (fasting adults) is about 4 to 6 mmol/l or 80 to 110 mg/dl. (where 4 mmol/l or 80 mg/dl is "optimal".) A subject with a consistent range above 7 mmol/l or 126 mg/dl is generally held to have hyperglycemia, whereas a consistent range below 4 mmol/l or 70 mg/dl is considered hypoglycemic. In fasting adults, blood plasma glucose should not exceed 7 mmol/l or 126 mg/dL. Sustained higher levels of blood sugar cause damage to the blood vessels and to the organs they supply, leading to the complications of diabetes.

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 %).

Diabetic ketoacidosis

In general, insulin is given at 0.1 unit/kg per hour to reduce the blood sugars and suppress ketone production. Guidelines differ as to which dose to use when blood sugar levels start falling; American guidelines recommend reducing the dose of insulin once glucose falls below 16.6 mmol/l (300 mg/dl) and UK guidelines at 14 mmol/l (253 mg/dl). Others recommend infusing glucose in addition to saline to allow for ongoing infusion of higher doses of insulin.

Ranson criteria

Acute pancreatitis not secondary to gallstones At admission: Blood glucose > 11.11 mmol/L (> 200 mg/dL) Age > 55 years Serum LDH > 350 IU/L Serum AST > 250 IU/L WBC count > 16000 cells/mm3 Within 48 hours: Serum calcium < 2.0 mmol/L (< 8.0 mg/dL) Hematocrit decreased by > 10% Oxygen (hypoxemia with PaO2 < 60 mmHg) BUN increased by 1.8 or more mmol/L (5 or more mg/dL) after IV fluid hydration Base deficit (negative base excess) > 4 mEq/L Sequestration of fluids > 6 L Acute pancreatitis secondary to gallstones At admission: Glucose > 220 mg/dl Age > 70 years LDH > 400 IU/L AST > 250 IU/ 100 ml WBC count > 18000 cells/mm3 Within 48 hours: Serum calcium < 8 mg/dL Hematocrit decreased by > 10% Base deficit > 4 mEq/L BUN increased by > 2 mg/dL Sequestered fluid > 6L

[Diabetic ketoacidosis (169 episodes in 131 patients in the course of 10 years)].

Diabetic patient material--presenting hyperglycaemic ketoacidotic episode--observed in Gyula and Szekszárd County Hospitals in period 1980-89, was reviewed by authors. 131 patients were admitted with 169 ketoacidotic episodes (among them 23 patients had 62 recurrences). The mean age of patients were 49.4 years (14-84 years), duration of diabetes 9.5 years (from one month to 45 years). The common cause of diabetic ketoacidosis was respiratory (26 per cent) and enteral (35.5 per cent) infection. The consciousness of patients had shown close correlation with the increase of blood sugar and urea nitrogen level as well as with the decreasing of the pH value of capillary blood. The first step of the therapy was the parenteral fluid intake with isotonic solution (in the first hour the average 1351 ml). In 18 patients fast-acting insulin (Novo Actrapid MC) was given by constant infusion, in the remaining cases intravenous or intramuscular low doses of the same insulin were administered. The importance of early potassium replacement, and the dangers of forced and rapid correction of acidosis is emphasized. Lethality related to episodes was 10 per cent, related to the patients 12.9 per cent. The number of ketoacidotic cases did not decrease parallel with the improvement of therapeutic possibilities, as it was experienced by their earlier evaluations. The importance of the prevention of acute metabolic disorders is outlined might be resulted from increasing the efficacy of patients education and better knowledge of GP's, as well.

Acute pancreatitis

At admission age in years > 55 years white blood cell count > 16000 cells/mm3 blood glucose > 11.1 mmol/L (> 200 mg/dL) serum AST > 250 IU/L serum LDH > 350 IU/L At 48 hours Calcium (serum calcium < 2.0 mmol/L (< 8.0 mg/dL) Hematocrit fall >10% Oxygen (hypoxemia PO2 < 60 mmHg) BUN increased by 1.8 or more mmol/L (5 or more mg/dL) after IV fluid hydration Base deficit (negative base excess) > 4 mEq/L Sequestration of fluids > 6 L The criteria for point assignment is that a certain breakpoint be met at any time during that 48 hour period, so that in some situations it can be calculated shortly after admission. It is applicable to both gallstone and alcoholic pancreatitis. Alternatively, pancreatitis can be diagnosed by meeting any of the following:[2] Alternative Ranson score Ranson's score of ≥ 8 Organ failure Substantial pancreatic necrosis (at least 30% glandular necrosis according to contrast-enhanced CT)

Severe diabetic ketoacidosis: the need for large doses of insulin.

A 21-year-old female with Type 1 diabetes mellitus (DM) presented in ketoacidosis. She received intravenous normal saline and insulin at 6 U/h and 1.26% sodium bicarbonate solution. After the blood glucose had fallen to 9.5 mmol/l, the saline infusion was changed to 5% glucose solution and the insulin infusion rate to 2 to 3 U/h. The next day the patient became more drowsy (Glasgow coma scale 13/15, later falling to 4/15). Computed tomography (CT) scan suggested cerebral oedema and the patient was treated with dexamethasone and mannitol. She remained critically ill for 48 h, eventually making a full recovery. Insulin was given at rates of 8 to 14 U/h, with 10% or 20% glucose infusion to maintain the blood glucose above 5 mmol/l; despite this it was not until the fifth day that her serum bicarbonate became normal. Textbooks usually advise starting insulin at 6 U/h and reducing the infusion rate to 1-4 U/h when the blood glucose falls below a certain level. In this case, even with high rates of insulin infusion, it took 5 days before the patient's serum bicarbonate returned to normal. Thus, in severe diabetic ketoacidosis (DKA), protocols should advise that the insulin infusion be continued at high dose (4 to 6 U/h or more), with appropriate glucose infusion to prevent hypoglycaemia, until the serum bicarbonate is normal or nearly so.

[Hyperglycemia controlled with GIK solution in non-diabetic patients subjected to heart surgery].

We prospectively compared, the glucose-insulin-potassium (GIK) solution 1,000 mL 10% glucose, 20 units of fast acting insulin and 60 mEq of potassium chloride, against a GIK solution with 1,000 mL of glucose, 40 units of fast acting insulin an 120 mEq of chloride, in the hyperglycemic control of non-diabetic patient subjected to cardiac surgery. We divided 40 patients in four groups ten patients each. Group A was the control they received 1,000 mL of 10% glucose in water, 20 units of fast acting insulin and 60 mEq of potassium chloride in a drops/ hour dose without an infusion pump. Group B received the same solution in a 50 mL/hour dose. Group C received 1,000 mL of 10% glucose in water, 40 units of fast acting insulin plus, 120 mEq of potassium chloride at the same infusion rate as Group A. Group D 2 1,000 mL of 10% of glucose in water, 40 units of fast acting insulin in the same rate as Group B. The GIK solution was started after anesthesia induction and maintained all along the extracorporeal circulation, the study continued until the patient was transferred to the intensive care unit. We measured blood glucose, circulating insulin and seric levels of potassium three times; basal before the anesthetic induction, during the extracorporeal circulation and at the intensive care unit arrival. The data were analyzed with measure of central tendency, dispersion and multivariate analysis. Among the four groups no statistically significant differences existed in demographic data. In Group A, glucose and potassium levels were higher as compared with the rest of the groups (p <0.05) in all measurements; Group D was less hyperglycaemic as compared with Groups A, B, and C. The solution with low insulin dose does useful plasmatic insulin levels in the hyperglycemia in non diabetic patients subjected to cardiac surgery.

InternalMed_Harrison

A bolus of IV (0.1 units/kg) short-acting insulin should be administered immediately (Table 418-8), and subsequent treatment should provide continuous and adequate levels of circulating insulin. IV administration is preferred (0.1 units/kg of regular insulin per hour) because it ensures rapid distribution and allows adjustment of the infusion rate as the patient responds to therapy. In mild episodes of DKA, short-acting insulin can be used SC. IV insulin mAnAgEmEnT of DiAbETiC kEToACiDoSiS 1. Confirm diagnosis (↑ plasma glucose, positive serum ketones, metabolic acidosis). 2. Admit to hospital; intensive care setting may be necessary for frequent monitoring or if pH <7.00 or unconscious. 3. Assess: Serum electrolytes (K+, Na+, Mg2+, Cl−, bicarbonate, phosphate) Acid-base status—pH, HCO3−, PCO2, β-hydroxybutyrate Renal function (creatinine, urine output) 4.

Ringer's lactate solution

In a large-volume resuscitation over several hours, LRS maintains a more stable blood pH than normal saline. Chemistry One liter of Ringer's lactate solution contains: 130–131 mEq of sodium ion = 130 mmol L−1 109–111 mEq of chloride ion = 109 mmol L−1 28–29 mEq of lactate ion = 28 mmol L−1 4–5 mEq of potassium ion = 4 mmol L−1 2–3 mEq of calcium ion = 1.5 mmol L−1 Ringer's lactate has an osmolarity of 273 mOsm L−1 and a pH of 6.5. The lactate is metabolized into bicarbonate by the liver, which can help correct metabolic acidosis. Ringer's lactate solution alkalinizes via its consumption in the citric acid cycle, the generation of a molecule of carbon dioxide which is then excreted by the lungs. They increase the strong ion difference in solution, leading to proton consumption and an overall alkalinizing effect.

Effect of 50 milliliters of 50% dextrose in water administration on the blood sugar of euglycemic volunteers.

To evaluate the effect of administration of 1 ampule of 50% dextrose in water solution (D50W) on serum glucose levels in healthy adult volunteers, the authors set out to determine whether a pre-D50W serum glucose level can be predicted from the ED sample. This was a prospective, interventional study conducted from the ED of an urban, university-affiliated hospital. All subjects were healthy employee volunteers between 25 and 40 years of age. Baseline serum glucose levels were determined and all subjects were given an i.v. bolus of 25 grams of 50% dextrose solution. The main outcome measures were post-D50W serum glucose levels (observed) at 5 predetermined time intervals (5 min, 15 min, 30 min, 1 hr, and 2 hr). An expected change in serum glucose was calculated using the volume of distribution formula for glucose. Twenty-five volunteers (17 males and 8 females) participated in the study. The mean baseline serum glucose was 82.3 +/- 13.5 mg/dL. The mean post-infusion levels were: 244.4 +/- 44.6 mg/dL (5 min), 145.8 +/- 52.3 mg/dL (15 min), 88.1 +/- 28.8 mg/dL (30 min), 77.6 +/- 13.6 mg/dL (60 min), and 83.2 +/- 11.4 mg/dL (120 min). Using a mixed-effect regression model, statistically significant increases in serum glucose levels were found at 5 minutes (p < 0.001) and 15 minutes (p < 00001) following administration of D50W. There was a return to baseline serum glucose by 30 minutes. The expected change based on the volume of distribution formula (53.7 +/- 34.9) did not correlate with the observed changes at any measured time interval. Without pre-intervention blood drawing by emergency medical services, it is not possible to accurately predict pre-D50W serum glucose levels based on post-D50W glucose levels. The diagnosis of hypoglycemia as the etiology of altered mental status must therefore remain a diagnosis of exclusion. In addition, the return of serum glucose to baseline after 30 minutes suggests the duration of the effect of 1 ampule of D50W. Frequent re-evaluation of the serum glucose levels of suspected or proven hypoglycemic patients after administration of D50W should be considered.

Blood sugar level

Normal blood glucose level (tested while fasting) for non-diabetics is between 3.9 and 7.1 mmol/L (70 and 130 mg/dL). The global mean fasting plasma blood glucose level in humans is about 5.5 mmol/L (100 mg/dL); however, this level fluctuates throughout the day. Blood sugar levels for those without diabetes and who are not fasting should be below 6.9 mmol/L (125 mg/dL). The blood glucose target range for diabetics, according to the American Diabetes Association, should be 5.0–7.2 mmol/l (90–130 mg/dL) before meals and less than 10 mmol/L (180 mg/dL) two hours after meals (as measured by a blood glucose monitor).

[Treatment of hyperglycemic coma states in diabetics].

In the treatment of acute decompensation of diabetes, diabetic ketoacidosis and hyperosmolar non-acidotic syndrome the basic demand is insulin administration--in small doses by the i.v. route, preferably by means of an injectomat in a permanent infusion. An alternative method for departments which do not possess a suitable infusion pump, is fractionated administration of small insulin amounts into the vein after 30 minute intervals. Equally important is rehydration treatment with saline; only in case of hypernatriaemia above 150 mmol/l the author recommends 0.45% NaCl. Acidosis in DKA is corrected by sodium bicarbonate only at pH 7.1 or less. As to K cations, the replacement of potassium ions is most important; the value of substitution of other cations (Ca, Mg) is doubtful and is not currently done, the same applies to phosphate anion replacement. It has not been proved that prevention of thromboembolic complications by heparin is expedient in these conditions.

Serum glucose changes after administration of 50% dextrose solution: pre- and in-hospital calculations.

A prospective clinical trial was conducted to estimate the rise in serum glucose level after an intravenous bolus of 50 ml of 50% dextrose solution (D-50) in the emergency department setting. Fifty one subjects with altered levels of consciousness were studied. Of these, 23 patients were known diabetics, and 28 were not diabetic. The change in glucose level for the total study group ranged from a low of 37 mg/dl to a high of 370 mg/dl, with a mean of 166 +/- 77 mg/dl. The mean for the diabetic and non-diabetic groups were 177 +/- 80 mg/dl and 154 +/- 75 mg/dl. These results suggest that serum glucose levels cannot be quantitatively predicted after a single intravenous bolus of D-50.

Adult Diabetic Ketoacidosis -- Evaluation

Commonly accepted criteria for diabetic ketoacidosis are blood glucose greater than 250 mg/dl, arterial pH less than 7.3, serum bicarbonate less than 15 mEq/l, and the presence of ketonemia or ketonuria. The normal anion gap is 12 mEq/l. Anion gap greater than 14-15 mEq/l indicates the presence of an increased anion gap metabolic acidosis. [17] Arterial pH may be normal or even raised if other types of metabolic or respiratory alkalosis coexist. Typical examples are vomiting or diuretic use. [18] Blood glucose may be normal or minimally elevated in patients with DKA (<300 mg/dl), where the underlying risk of hypoglycemia preexists, such as in patients with alcohol use disorder or patients receiving insulin or SGLT2 inhibitors.

Blood sugar level

Despite widely variable intervals between meals or the occasional consumption of meals with a substantial carbohydrate load, human blood glucose levels tend to remain within the normal range. However, shortly after eating, the blood glucose level may rise, in non-diabetics, temporarily up to 7.8 mmol/L (140 mg/dL) or slightly more. For people with diabetes maintaining "tight diabetes control", the American Diabetes Association recommends a post-meal glucose level of less than 10 mmol/L (180 mg/dL) and a fasting plasma glucose of 3.9 to 7.2 mmol/L (70–130 mg/dL). The actual amount of glucose in the blood and body fluids is very small. In a healthy adult male of with a blood volume of 5 L, a blood glucose level of 5.5 mmol/L (100 mg/dL) amounts to 5 g, equivalent to about a teaspoonful of sugar. Part of the reason why this amount is so small is that, to maintain an influx of glucose into cells, enzymes modify glucose by adding phosphate or other groups to it. Other animals

Just the Facts: Diagnosis and treatment of diabetic ketoacidosis in the emergency department.

A 21-year-old male with known type 1 diabetes mellitus presented to the emergency department (ED) with two days of vomiting, polyuria, and polydipsia after several days of viral upper respiratory tract infection symptoms. Since his symptom onset, his home capillary blood glucose readings have been higher than usual. On the day of presentation, his glucometer read "high," and he could not tolerate oral fluids. On examination, his pulse was 110 beats/minute, and his respiratory rate was 24 breaths/minute. He was afebrile, and the remaining vital signs were normal. Other than dry mucous membranes, his cardiopulmonary, abdominal, and neurologic exams were unremarkable. Venous blood gas demonstrated a pH of 7.25 mm Hg, pCO2 of 31 mm Hg, HCO3 of 13 mm Hg, anion gap of 18 mmol/L, and laboratory blood glucose of 40 mmol/L, as well as serum ketones measuring "large."


The most influential cardiovascular factor for stroke in women over 70 is blood pressure.

A 76-year-old woman consults us because she is concerned about her risk of stroke since her mother died of stroke a year ago. She is diagnosed with arterial hypertension and type 2 diabetes mellitus and is being treated with glipizide, aspirin, enalapril and atorvastatin. She smokes 20 cigarettes a day and leads a sedentary life. The examination revealed a blood pressure of 150/80 mm Hg. The blood test shows a hemoglobin A1C of 8% and LDL cholesterol of 110 mg/dl. Which of the following actions is associated with a greater reduction in the risk of stroke?

Intensive glycaemic control in type 2 diabetes mellitus: does it improve cardiovascular outcomes?

With growing urbanization and economic development, there is a rapid increase in the incidence of type 2 diabetes mellitus (T2DM) in India. T2DM is associated with 2-4 times higher risk for cardiovascular disease (CVD), including coronary artery disease, stroke and peripheral vascular disease. Several studies have shown the benefit of intensive glycaemic control in reducing the frequency of diabetic microvascular complications such as retinopathy and nephropathy. Results of long term follow up of patients with diabetes, who were enrolled in earlier trials, have shown that initial intensive glycaemic control led to a reduction in CVD outcomes when compared with standard therapy. However, it is unclear if intensive glycaemic control, aiming to reduce haemoglobin A1c to levels even lower than the current goal of <7%, will similarly lead to reduction in the rates of CVD. Recently, the results of 3 large, randomized controlled trials have been published, which suggest that in established T2DM with previous CVD or high risk of CVD, the benefits of intensive glycaemic control when compared with conventional good control, are minimal with regards to reduction of cardiovascular outcomes. Intensive therapy increases the risk of side-effects such as severe hypoglycaemia and weight gain. The implementation of such a therapy, with rigorous attention to frequent monitoring of blood glucose and visits to the physician, is not likely to be possible on a large scale, especially in a developing country such as India. The aim of management of patients with established T2DM should be to achieve the goal of good glycaemic control (haemoglobin A1c<7%), with avoidance of hypoglycaemia. It is equally, if not more important, to control other risk factors of CVD by paying greater attention to lifestyle measures (weight loss if overweight or obese, regular exercise, cessation of smoking), rigorous control of blood pressure (<130/80 mmHg) and low density lipoprotein (LDL) cholesterol (<100 mg/dl or <70 mg/dl if already diagnosed with CVD) and the prophylactic use of low dose aspirin as per current recommendations. A multifactorial approach targeting multiple cardiovascular risk factors is likely to be most effective in reducing CVD outcomes in T2DM.

Care of adults with type 2 diabetes mellitus. A review of the evidence.

The purpose of this study was to provide primary care physicians with a concise review of the evidence that guides selected aspects of type 2 diabetes care, including glycemic control, macrovascular risk reduction, and screening for microvascular complications of diabetes. We identified randomized clinical trials that addressed selected aspects of the care of adults with type 2 diabetes using systematic literature review, review of existing clinical guidelines, and other sources. The results of these trials were interpreted as absolute risk reduction, and the number of patients that need to be treated to obtain a specific clinical outcome was calculated. Good glycemic control with metformin may reduce overall mortality in obese patients with type 2 diabetes (number need to treat [NNT] = 14 for 10 years), and improved blood pressure control reduced diabetes-related mortality (NNT = 15 for 10 years); improved glycemic control with agents other than metformin, or with combinations including metformin, does not reduce diabetes-related or overall mortality. Major cardiovascular events (CVE) in type 2 diabetes can be prevented by control of blood pressure with low-dose diuretics, atenolol, or angiotensin-converting enzyme inhibitors (NNT = 10 to 20 for 5 to 10 years for primary prevention of one CVE); by use of aspirin (NNT = 45 for 5 years for primary prevention of one CVE); and by use of simvastatin to lower low-density lipoprotein (LDL) cholesterol (NNT = 6 for 5 years for secondary prevention of one CVE). Glycemic control (NNT = 19 for 10 years) and hypertension control (NNT = 6 for 10 years) slow the progression of complications in patients with type 2 diabetes. Retinopathy and nephropathy are more preventable than neuropathy. The benefits of glycemic control are less for patients with shorter life expectancy and are greater for those with the highest levels of Hb A1c because larger Hb A1c improvements can be achieved in such patients. Periodic screening of patients for eye, kidney, and foot complications is supported because effective early treatment of these complications is available. In patients with type 2 diabetes, control of hypertension reduces microvascular and macrovascular complications more than glycemic control does. Control of LDL cholesterol with statins, aspirin, and smoking cessation reduce major cardiovascular events. Metformin reduces overall mortality in obese patients with creatinine levels < 1.5 mg/dL. Glycemic control reduces microvascular complications. The evidence supports angiotensin-converting enzyme inhibitors, atenolol, or low-dose diuretics for blood pressure control. Effective treatment of eye, kidney, and foot complications is available, and regular screening for these complications is justified.

[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.

Type 2 diabetes: Which interventions best reduce absolute risks of adverse events?

Benefits of interventions are usually reported as relative risk reductions. Absolute risk reductions (ARRs)-most relevant to individual patients-are reported less often. Estimate ARRs for interventions in a patient with diabetes mellitus. We used the Archimedes Risk Assessment Tool to estimate 10-year risks of myocardial infarction (MI), cerebrovascular accident (CVA), end-stage renal disease (ESRD), blindness, foot ulceration, and amputation, and to estimate the ARRs associated with controlling blood pressure (BP), blood sugar, and low-density lipoprotein (LDL) cholesterol levels; moderate exercise; and taking aspirin and a beta-blocker. Our hypothetical base case was a 65-year-old white man. Three other hypothetical patients were a 50-year-old white man, a 65-year-old white woman, and a 65-year-old black man. Each patient had a 5-year history of diabetes mellitus, a sedentary lifestyle, body mass index (BMI) of 28 kg/m2, BP of 140/90 mm Hg, LDL of 120 mg/dL, high-density lipoprotein (HDL) of 45 mg/dL, and glycosylated hemoglobin (HbA1c) of 10%. For the base case, the risks of MI (22.3%) and CVA (14.4%) far exceeded the risks of ESRD, blindness, and amputation. ARRs for interventions to reduce MI risk were: aspirin, 6.8%; HbA1c to 7%, 5.1%; moderate exercise, 2.7%; BP to 130/80 mm Hg, 1.4%; and LDL to 100 mg/dL, 1.4%. The female patient had a lower ARR for aspirin and a greater ARR for exercise. The black male patient had greater ARRs for both aspirin and exercise. Estimates were similar for CVA. Patients resembling our base case and its variations would probably benefit more from aspirin and moderate exercise than from all other interventions combined.

Rationale, Design, and Implementation of Intensive Risk Factor Treatment in the CREST2 Trial.

The CREST2 trial (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis) is comparing intensive medical management (IMM) alone to IMM plus revascularization with carotid endarterectomy or transfemoral carotid artery stenting for preventing stroke or death within 44 days after randomization or ipsilateral ischemic stroke thereafter. There are extensive clinical trial data on outcomes after revascularization of asymptomatic carotid stenosis, but not for IMM. As such, the experimental treatment in CREST2 is IMM, which is described in this article. IMM consists of aspirin 325 mg/day and intensive risk factor management, primarily targeting systolic blood pressure <130 mm Hg (initially systolic blood pressure <140 mm Hg) and LDL (low-density lipoprotein) cholesterol <70 mg/dL. Secondary risk factor targets focus on tobacco smoking, non-HDL (high-density lipoprotein), HbA1c (hemoglobin A1c), physical activity, and weight. Risk factor management is performed by site personnel and a lifestyle coaching program delivered by telephone. We report interim risk factor data on 1618 patients at baseline and last follow-up through 24 months. The mean baseline LDL of 80.5 mg/dL improved to 66.7 mg/dL. The mean baseline systolic blood pressure of 139.7 mm Hg improved to 130.3 mm Hg. The proportion of patients in-target improved from 43% to 61% for systolic blood pressure <130 mm Hg and from 45% to 67% for LDL<70 mg/dL (both changes <iP</i<0.001). The rigorous multimodal approach to intensive stroke risk factor management in CREST2 has resulted in significant improvements in risk factor control that will enable a comparison of cutting-edge medical care to revascularization in patients with asymptomatic carotid stenosis. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02089217.

Intensive statin therapy for Indians: Part-I. Benefits.

The underlying disorder in the vast majority of cases of cardiovascular disease (CVD) is atherosclerosis, for which low-density lipoprotein cholesterol (LDL-C) is recognized as the first and foremost risk factor. HMG-CoA reductase inhibitors, popularly called statins, are highly effective and remarkably safe in reducing LDL-C and non-HDL-C levels. Evidence from clinical trials have demonstrated that statin therapy can reduce the risk of myocardial infarction (MI), stroke, death, and the need for coronary artery revascularization procedures (CARPs) by 25-50%, depending on the magnitude of LDL-C lowering achieved. Benefits are seen in men and women, young and old, and in people with and without diabetes or prior diagnosis of CVD. Clinical trials comparing standard statin therapy to intensive statin therapy have clearly demonstrated greater benefits in CVD risk reduction (including halting the progression and even reversing coronary atherosclerosis) without any corresponding increase in risk. Numerous outcome trials of intensive statin therapy using atorvastatin 80 mg/d have demonstrated the safety and the benefits of lowering LDL-C to very low levels. This led the USNCEP Guideline Committee to standardize 40 mg/dL as the optimum LDL-C level, above which the CVD risk begins to rise. Recent studies have shown intensive statin therapy can also lower CVD events even in low-risk individuals with LDL-C <110 mg/dL. Because of the heightened risk of CVD in Asian Indians, the LDL-C target is set at 30 mg/dL lower than that recommended by NCEP. Accordingly, the LDL-C goal is < 70 mg/dL for Indians who have CVD, diabetes, metabolic syndrome, or chronic kidney disease. Intensive statin therapy is often required in these populations as well as others who require a > or = 50% reduction in LDL-C. Broader acceptance of this lower LDL-C targets and its implementation could reduce the CVD burden in the Indian population by 50% in the next 25 years. Clinical trial data support an extremely favorable benefit-to-risk ratio of intensive statin therapy with some but not all statins. Atorvastatin 80 mg/d is 100 times safer than aspirin 81 mg/d and 10 times safer than diabetic medications. Intensive statin therapy is more effective and safe compared to intensive control of blood sugar or blood pressure in patients with diabetes.

Treatment of cardiac risk factors in diabetic patients: How well do we follow the guidelines?

Diabetic patients are at increased risk for both macrovascular and microvascular disease compared with nondiabetic patients. We conducted a prospective observational study to assess the control of multiple predetermined cardiovascular risk factors in 235 treated diabetic patients undergoing elective cardiac catheterization at our institution between December 20, 1997, and February 15, 2000. The following parameters were used to define optimal treatment in these patients: hemoglobin (Hgb) A1c <7%, low-density lipoprotein cholesterol (LDL-c) <100 mg/dL, high-density lipoprotein cholesterol (HDL-c) >/=45 mg/dL for men and >/=55 mg/dL for women, triglyceride (TG) level <200 mg/dL, blood pressure (BP) <130/85 mm Hg, body mass index (BMI) <25, daily aspirin therapy, and current nonsmoking status. The use of b-blockers and angiotensin-converting enzyme inhibitors was also evaluated. The average patient age was 64 +/- 11 years; 155 (65%) were male. One hundred ninety-one (81%) patients had documented coronary artery disease at cardiac catheterization. The mean Hgb A1c level for all diabetic patients was 8.2% +/- 1.6%. Overall, 49 (21%) had an Hgb A1c level <7%. The fasting cholesterol panel for all patients revealed a mean LDL-c level of 103 +/- 41 mg/dL, a mean HDL level of 39 +/- 11 mg/dL, and a mean TG level of 164 +/- 128 mg/dL. One hundred sixteen (52%) patients had an LDL-c <100 mg/dL. Only 32 of 147 (22%) male patients and 14 of 80 (18%) female patients achieved an HDL-c >/=45 mg/dL or >/=55 mg/dL, respectively. One hundred seventy-seven of 232 (76%) patients had a TG level <200 mg/dL. Only 23 of 233 (10%) diabetics were controlled to a BP of <130/85 mm Hg, and 25 (11%) achieved a BMI <25. Only one patient (0.4%) had optimal control of all modifiable risk factors. These data demonstrate the poor control of numerous cardiovascular risk factors in treated diabetics undergoing elective cardiac catheterization.

Achievement of optimal medical therapy goals for U.S. adults with coronary artery disease: results from the REGARDS Study (REasons for Geographic And Racial Differences in Stroke).

In a nonclinical trial setting, we sought to determine the proportion of individuals with coronary artery disease (CAD) with optimal risk factor levels based on the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive DruG Evaluation) trial. In the COURAGE trial, the addition of percutaneous coronary intervention (PCI) to optimal medical therapy did not reduce the risk of death or myocardial infarction in stable CAD patients but resulted in more revascularization procedures. The REGARDS (REasons for Geographic And Racial Differences in Stroke) study is a national prospective cohort study of 30,239 African-American and white community-dwelling individuals older than 45 years of age who enrolled in 2003 through 2007. We calculated the proportion of 3,167 participants with self-reported CAD meeting 7 risk factor goals based on the COURAGE trial: 1) aspirin use; 2) systolic blood pressure <130 mm Hg and diastolic blood pressure <85 mm Hg (<80 mm Hg if diabetic); 3) low-density lipoprotein cholesterol <85 mg/dl, high-density lipoprotein cholesterol >40 mg/dl, and triglycerides <150 mg/dl; 4) fasting glucose <126 mg/dl; 5) nonsmoking status; 6) body mass index <25 kg/m(2); and 7) exercise ≥4 days per week. The mean age of participants was 69 ± 9 years; 33% were African American and 35% were female. Overall, the median number of goals met was 4. Less than one-fourth met ≥5 of the 7 goals, and 16% met all 3 goals for aspirin, blood pressure, and low-density lipoprotein cholesterol. Older age, white race, higher income, more education, and higher physical functioning were independently associated with meeting more goals. There is substantial room for improvement in risk factor reduction among U.S. individuals with CAD.

Prevention of coronary heart disease. Part I. Primary prevention.

The first concern in primary prevention is the physician's belief that primary prevention is important for all adults and that intervention can significantly affect risk. Given the coronary plaque burden over many years and the importance of the development of healthy lifestyles early in adulthood to decrease coronary plaque burden, there are excellent reasons to begin prevention even with young adults. At the very least, a patient seen for any reason should provide a smoking history, have knowledge of the presence of early CHD in first-degree relatives and measurements of blood pressure, height, and weight, provide evidence for a cholesterol level within 5 years (after age 20 according to NCEP guidelines or in middle age according to ACP guidelines), and be given an assessment of glucose tolerance or diabetes. Information about alcohol intake and physical activity status are also of some importance. Other than height, weight, and blood pressure, during the physical examination, the physician should initially assess the strength of pulses in the lower extremities, evidence for carotid or femoral bruits, and eyegrounds for retinal arterial changes, and the skin and subcutaneous tissue should be examined for xanthomas and the eyes should be examined for corneal arcus and xanthelesma. These elements should be part of any initial examination by a primary care physician and are not extraordinary. In addition to lipid and blood sugar analyses, other evaluations may include blood urea nitrogen and creatinine and electrolytes in patients with hypertension or diabetes or in patients who are on antihypertensive agents. It may be prudent to obtain an ECG for patients who are older than 40 years. The elements mentioned above are the elements of the history, physical examination, and laboratory examination in subjects without a past history of CHD and with no clinical evidence for CHD. Primary prevention management begins with a discussion of risk factors with the patient. The key interventions aim at the lowering of blood pressure to at least less than 140/90 mm Hg, the complete cessation of smoking, the lowering of lipid levels to less than 130 mg/dL, the lowering of triglycerides to less than 200 mg/dL (or, some would argue, < 150 mg/dL), and the attempt to keep HDL cholesterol above 35 mg/dL (more than 40 to 45 mg/dL is a better goal) with the use of lifestyle modification. For patients with diabetes, strict control of glucose levels is essential to minimize disease of the microvasculature and possibly to minimize progressive renal disease. There are several lifestyle modifications for lipids. For patients with elevated LDL cholesterol, modifications include a less than 30% fat calorie diet and less than 300 mg of cholesterol intake daily, with fat calories approximately equally distributed among saturated fats, polyunsaturated fats, and monounsaturated fats (1/3, 1/3, 1/3; rule of 3s). The assistance of a dietician is extremely helpful in this regard. For patients with a low HDL cholesterol, weight reduction (for overweight patients) by calorie control and increased physical activity and smoking cessation will have some modest effect. For patients with elevated triglycerides, a diet similar to that for lowering of LDL cholesterol with the addition of stricter calorie limitation, avoidance of refined sugars, increase in complex carbohydrates, and avoidance of alcohol will be helpful. A decrease in the percent of fat calories to 20% to 25% will be of assistance to those patients with particularly high triglycerides. The treatment of underlying conditions such as diabetes mellitus, hypothyroidism, liver disease, and some renal conditions may also significantly modify high triglycerides. For patients with hypertension, limitation of sodium to 2 gm/d (6 gm sodium chloride), limitation of alcohol to 1 to 2 drinks a day, increased physical activity, and weight reduction are the key lifestyle modifications. (ABSTRACT TRUNCATED)

Secondary prevention advices after cardiovascular index event: From drug prescription to risk factors control in real world practice.

The present study aims at evaluating the achievement of blood pressure, lipid and blood glucose targets, healthy lifestyle changes and appropriate drug prescription/adherence in patients attending secondary prevention/CR ambulatory visit after index cardiovascular event in a time period ranging 1 to 5 year. At ambulatory visit, a predetermined set of data collection was used, including demographic data, cardiovascular risk factors and lifestyle habits, type and time of index event, current symptoms, physical sign, biochemistry and current medical treatment (including type and dosage). Cardiovascular risk profile (smoking habits, physical activity and body weight), secondary prevention goals (LDL-cholesterol, blood pressure, resting heart rate, glycated haemoglobin level) and the use of recommended drugs were also evaluated and categorized. Study population consisted of 800 patients [644 men (84.5%), aged 69±10.9 years)]. Cardiovascular index events were coronary artery bypass graft (CABG) (20%) ST segment elevation myocardial infarction (STEMI) (28%), non-ST segment elevation myocardial infarction (NSTEMI) (21%) and stable angina (13%) by unstable angina (13%) and stroke (5%). About 30% of patients was symptomatic (angina or dyspnoea) at the time of ambulatory visit. Major comorbidities were hypertension (73%), dyslipidaemia (64%) and diabetes (40%). More than 80% of patients achieved target levels for blood pressure. Patients that have participated to cardiac rehabilitation programmes after cardiovascular index event showed best achievement in blood pressure target (83.8% vs 76.8%, p=0.02). LDL-cholesterol target (<70 mg/dl) was achieved in about 2/3 of patients; HbA1c target (<7%) was achieved in 56.4% of diabetic population. About 75% of study cohort was treated with RAAS inhibitors, 85% with beta-blockers, 92% with statins and 87% with acetylsalicylic acid. All drugs were increasingly adopted from index event. Implementing secondary prevention guidelines into the 'real world' clinical practice in "late" interval from 1 to 5 years after a cardiovascular event improved risk factors control and appropriate drug prescription. Whether these improvements translated into prognostic advantages remains to be elucidated.

Polycap

To be included in the study, patients had to be at intermediate risk for myocardial infarction, stroke, and cardiovascular death. The participants’ average age was 64 years. Men 50 years and older and women 55 years and older with an INTERHEART risk score ≥ 10 (or men and women 65 years and older with an INTERHEART risk score ≥ 5) were included in the international study. Roughly 53% of study participants were women. Mean LDL cholesterol level and systolic blood pressure at baseline were 121 mg/dL and 144.5 mm Hg, respectively. For the trial, participants were randomly assigned to one of four groups. They were asked to take one of the following daily: both the polypill and aspirin, the polypill alone, aspirin alone, or only a placebo. The top-enrolling countries were India, the Philippines, Columbia, and Bangladesh; Canada enrolled 131 patients. Medications included in the polypill were atenolol, 100 mg; ramipril, 10 mg; hydrochlorothiazide, 25 mg; and simvastatin, 40 mg.

Gynecology_Novak

Figure 9.4 is a suggested algorithm for cholesterol control based on LDL levels. Cholesterol fat-lowering diet books abound in most bookstores and allow the patient to choose a diet she will best follow. The role of exercise and cigarette cessation should be stressed to all patients. Patients with a family history of cardiovascular disease (history of premature coronary artery problems and strokes) should be tested and started on conservative programs in their 20s. After 3 to 6 months, if the LDL remains above 160 mg/dL with zero to one risk factor or above 130 mg/dL with two or more risk factors, then medical therapy should be initiated. Any woman with coronary heart disease or equivalents such as diabetes or other forms of atherosclerotic disease (peripheral arterial disease, abdominal aortic aneurysm, and symptomatic carotid artery disease) should initiate lifestyle changes if her LDL is 100 mg/dL or more and drug therapy if her LDL is 130 mg/dL or more. Anyone with an LDL 190

Distribution of traditional and novel risk factors and their relation to subsequent cardiovascular events in patients with acute coronary syndromes (from the PROVE IT-TIMI 22 trial).

Current guidelines recommend risk stratification largely based on traditional risk factors such as those in the Framingham Risk Score. We studied the distribution of 12 traditional and non-traditional risk markers (age > or =65 years, male gender, family history of premature coronary heart disease, low-density lipoprotein cholesterol > or =70 mg/dl, high-density lipoprotein cholesterol <40 mg/dl in men and <50 mg/dl in women, systolic blood pressure >130 mm Hg, diabetes mellitus, smoking, C-reactive protein > or =2 mg/L, triglycerides >150 mg/dl, prediabetes defined as a fasting glucose level 100 to 125 mg/dl or hemoglobin A1c >6, and obesity defined as body mass index > or =30 kg/m(2)) in 3,675 patients from the PROVE IT-TIMI 22 trial at 4 months and evaluated the risk of cardiovascular events stratified by the number of risk factors. The median number of risk factors was 5. In individual risk factor subgroups, men, smokers, hypertensives, and patients with increased low-density lipoprotein cholesterol had just that added risk factor compared to their counterparts (median 5 vs 4). In contrast, patients with diabetes, prediabetes, and increased triglycerides, C-reactive protein, or body mass index had not only that, but also another added risk factor (median 6 vs 4). A higher risk factor count was strongly related with increased rate of death, myocardial infarction, unstable angina, stroke, or revascularization, from 0% to 38.6% at 2 years for 0 to > or =9 risk factors (p <0.0001). In conclusion, with the observed "clustering" of risk factors and the link between increasing risk factor count and adverse outcomes in a patient with 1 diagnosed risk factor, a comprehensive review of traditional and novel risk factors is important to fully assess cardiovascular risk.

Pharmacology_Katzung

A 53-year-old woman with a history of knee osteoarthritis, high cholesterol, type 2 diabetes, and hypertension presents with new onset of hot flashes and a question about a dietary supplement. She is obese (body mass index [BMI] 33), does not exercise, and spends a good portion of her work day in a seated position. She eats a low-sugar diet and regularly eats packaged frozen meals for dinner because she doesn’t have time to cook regularly. Her most recent laboratory values include a low-density lipoprotein (LDL) cholesterol that is above goal at 160 mg/dL (goal < 100 mg/dL) and a hemo-globin A1c that is well controlled at 6%. Her blood pressure is high at 160/100 mm Hg. Her prescription medications include simvastatin, metformin, and benazepril. She also takes over-the-counter ibuprofen for occasional knee pain and a multivitamin supplement once daily. She has heard good things about natural products and asks you if taking a garlic supplement daily could help to bring her blood

Effect of Multifactorial Treatment Targets and Relative Importance of Hemoglobin A1c, Blood Pressure, and Low-Density Lipoprotein-Cholesterol on Cardiovascular Diseases in Chinese Primary Care Patients With Type 2 Diabetes Mellitus: A Population-Based Retrospective Cohort Study.

The relative effect of hemoglobin A1c, blood pressure, and low-density lipoprotein-cholesterol (LDL-C) ("ABC" factors) on the prevention of cardiovascular diseases (CVD) among patients with type 2 diabetes mellitus is poorly understood. This study aimed to evaluate the association of key clinical parameters on CVD risk using a multifactorial optimal control approach in Chinese primary care patients with type 2 diabetes mellitus. A population-based retrospective cohort study was conducted on 144 271 Chinese type 2 diabetes mellitus primary care patients, aged 18 to 79 and without prior clinical diagnosis of CVD in 2008-2011. Cox regressions were conducted to examine the association between the combinations of ABC targets (hemoglobin A1c <7%, blood pressure <130/90 mm Hg, and LDL-C <2.6 mmol/L) and risks of CVD (overall), coronary heart disease, stroke, and heart failure. Achieving more ABC targets incrementally reduced the incidence of total CVD and individual disease including coronary heart disease, stroke, and heart failure, irrespective of other patient characteristics. Compared with suboptimal control in all ABC levels, achieving any 1, 2, and all 3 ABC targets reduced the relative risk of CVD by 13% to 42%, 31% to 52%, and 55%, respectively. Among those achieving only 1 ABC target, LDL-C reduction was associated with the greatest CVD risk reduction (42%), followed by blood pressure reduction (18%), and hemoglobin A1c reduction (13%). To achieve the greatest risk reduction for the incidence of CVD, the ultimate goal of treatment should be to achieve target control of hemoglobin A1c, blood pressure, and LDL-C. If it is not possible to achieve all 3 targets, efforts should be prioritized on treating the LDL-C to minimize CVD risk.

[Control of cardiovascular risk factors in patients after myocardial infarction].

Despite significant improvements in the diagnosis and treatment of cardiovascular diseases that have occurred in recent years, they remain the main cause of morbidity and mortality in the population. In many European countries, the incidence of coronary heart disease is currently 50% lower than it was in the early 1980s, which is the result of cardiovascular prevention. A special group of patients are people after myocardial infarction with very high cardiovascular risk. They should definitely implement activities at the individual level e. g. work on improving the unhealthy lifestyle and pharmacologically control other risk factors. A diet low in saturated fats should be recommended, i.e. mainly containing whole grains, vegetables, fruits and fish, recommend regular physical exercise: 150 min / week of moderate, aerobic physical activity, reducing the supply of calories in order to get rid of overweight or obesity. Help in quitting tobacco addiction should take place through the minimal nicotine intervention and, if necessary, pharmacological therapy. Another thing is the control of other risk factors, i. e. the appropriate treatment of dyslipidemia (the primary target is LDL cholesterol <1.8 mmol/l or reduction by ≥ 50%, if the initial concentration is between 1.8 and 3.5 mmol/l, treatment hypertension (target arterial pressure for most people aged 18-65 is in the range: 120-130/70-79 mmHg, if it is well tolerated, while for older people it is in the range: 130-139/70-79mmHg, if it is well tolerated), optimal diabetes therapy (target glycated hemoglobin <7%) and appropriate antiplatelet therapy (in most patients double antiplatelet therapy is recommended for 12 months after acute coronary syndrome). These activities lead to a significant improvement in quality of life and a decrease in mortality due to cardiovascular diseases.

Surgery_Schwartz

statement summarize the secondary prevention recommendations.37 Class I recommendations include smoking cessation and avoid-ance of environmental tobacco exposure, blood pressure con-trol to under 140/90 mmHg (under 130/80 mmHg in those with diabetes or chronic kidney disease), LDL cholesterol levels less than 100 mg/dL, aspirin therapy in all patients without contra-indications, a BMI target of less than 25 kg/m2, diabetes man-agement with target HbA1c <7%, and encouragement of daily moderate-intensity aerobic exercise. β-Blockers should be used in all patients with LV dysfunction and following MI, ACS, or revascularization, unless a specific contraindication is pres-ent. Renin-angiogensin-aldosterone system blockade in patients with hypertension, LV dysfunction, diabetes, or chronic kidney disease should also be considered.Clinical ManifestationsPatients with CAD may have a spectrum of presentations, including angina pectoris, myocardial infarction, ischemic heart failure,

Green tea

Glycemic control Green tea consumption lowers fasting blood sugar but in clinical studies the beverage's effect on hemoglobin A1c and fasting insulin levels was inconsistent. Hyperlipidemia Drinking green tea or taking green tea supplements decreases the blood concentration of total cholesterol (about 3–7 mg/dL), LDL cholesterol (about 2 mg/dL), and does not affect the concentration of HDL cholesterol or triglycerides. A 2013 Cochrane meta-analysis of longer-term randomized controlled trials (>3 months duration) concluded that green tea consumption lowers total and LDL cholesterol concentrations in the blood. Inflammation A 2015 systematic review and meta-analysis of 11 randomized controlled trials found that green tea consumption was not significantly associated with lower plasma levels of C-reactive protein levels (a marker of inflammation). Weight loss There is no good evidence that green tea aids in weight loss or weight maintenance.

The Bucharest Multifactorial Prevention Trial of Coronary Heart Disease--ten year follow-up: 1971-1982.

The trial begun in 1971 and the paper brings the results after a ten-year follow-up. Both the intervention and control group contained 5000 men with a similar socioeconomic and professional structure; the intervention group was examined every six months in the first 5 years and annually in the second phase. The control group was examined "only after" 5 years and a second time at the final moment. The decreases of the cumulative ten-year incidences were: for hard events--26.7%; for myocardial infarction--20%; for fatal myocardial infarction--52%; for stroke--31%; for cardiovascular mortality--38%; for total mortality--14%. The trend of serum cholesterol and cigarettes/day was downward, but the blood pressure had a rather flat evolution in the intervention group. The control group disclosed also some downward trends.

Cardiovascular disease in women with diabetes mellitus: a review.

To analyze cardiovascular disease (CVD) along wit it's contributing risk factors in women with diabetes mellitus (DM) and from this, to recommend prevention strategies. A review of pertinent studies serves as the basis for the analysis and recommendations of prevention strategies in this group. Women with (DM) show a higher morbidity and mortality from CVD. The presence of DM confers these individuals the same risk of having a coronary event as present in a non-diabetic person who has suffered a previous myocardial infarction. Arterial hypertension, a characteristic dyslipidaemia (hypertrigliceridemia, low level of high density lipoprotein cholesterol and elevated low density lipoprotein cholesterol), obesity, microalbuminuria, platelet hyperaggregability and endothelial dysfunction converge conferring the women with DM a higher susceptibility to atherosclerosis. Recommendations include: lifestyle intervention weight reduction, increase in physical activity and smoking cessation. Women with DM should target to lower the LDL-C to a level below 100 mg/dl, the blood pressure level to below 130/80 mm Hg and triglycerides to less than 150 mg/dl. The goal is to raise HDL-C to a level over 45 mg/dl and reduce hemoglobin A1c (HbAlc) levels to below seven (7%) percent. Women with DM should use aspirin on a daily basis, unless contraindicated. These actions may lead to the reduction of the burden of CVD in women with DM. This article summarizes the recent salient features of CVD in women with DM with emphasis on preventive measures as well as on the understanding of prevailing guidelines established under the principles of evidence based medicine.

CARDS on the table: should everybody with type 2 diabetes take a statin?

Vascular complications are a major cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). The recently published Collaborative Atorvastatin Diabetes Study (CARDS) showed that atorvastatin (10 mg, once daily vs. placebo) markedly reduces vascular events in this high-risk population. The participants (n = 2838) were fairly typical T2DM = 2838) patients without cardiovascular disease and with at least one other risk factor: hypertension, retinopathy, albuminuria or current smoking. In the treatment group, coronary events were reduced by 36% (p = 0.001) and stroke by 48% (p = 0.001). The trial was terminated two years early on ethical grounds. The number needed to treat (NNT) was 27 for four years to prevent one event. However, the benefit may have been greater since a proportion of the placebo group received statin therapy. The benefit from statin treatment was independent of sex, age, baseline lipid levels, was independent of sex, age, baseline lipid levels, systolic blood pressure, retinopathy, albuminuria, systolic blood pressure, retinopathy, albuminuria, smoking or HbA smoking or HbA(1c). The frequency of adverse events did not differ between the groups. These findings support those of other statin trials. CARDS does not comment on renal function. However, other trials suggest that statins preserve renal function in those with and without DM. We discuss the CARDS study in this context in this brief overview paper. the evidence shows that we need to control glucose to prevent microvascular complications, to lower cholesterol to prevent macrovascular disease and to lower blood pressure to prevent both. It may be that the benefit of statins extends beyond a threshold low-density lipoprotein cholesterol level in patients with T2DM. More trials are needed in this field.

Secondary prevention of coronary heart disease in elderly patients.

Coronary heart disease remains a leading cause of mortality in the United States, with 84 percent of persons 65 years or older dying from this disease. Secondary preventive measures, including lifestyle modification and pharmacotherapy, are important for elderly patients because of the variable impacts on morbidity and mortality rates and quality of life. Participating in light to moderate activities significantly decreases mortality rates in elderly patients. Smoking cessation translates into a reduction in overall mortality and morbidity rates at least equal to that of other preventive measures such as aspirin or beta-blocker therapy. Recent studies on the effects of lowering low-density lipoprotein cholesterol levels to below 100 mg per dL have shown a substantial reduction in coronary heart disease mortality and nonfatal myocardial infarction rates, with a persistent effect in patients older than 75 years. Hypertension, manifesting mostly as isolated systolic blood pressure elevation, also should be treated aggressively. Conventional medical therapies for hypertension (e.g., diuretics, beta blockers) and newer agents (e.g., calcium channel blockers, angiotensin-converting enzyme inhibitors), together with sodium restriction, have had a positive effect on cardiovascular mortality and morbidity rates in older patients. With the increasing prevalence of obesity, insulin resistance, and type 2 diabetes, interventions targeting weight reduction and glucose control should be emphasized. Whereas weight-loss strategies are poorly defined in this population, the management of diabetes through dietary modification, exercise, and medications is similar across age groups. The target hemoglobin A1C level is less than 7 percent. Elderly patients are prone to depression and social isolation, and they are more likely to have a lower socioeconomic status than younger patients, which may negatively affect participation in rehabilitation programs and compliance with medical advice and therapy. Strategies aimed at these factors have shown variable results and remain ill-defined.

Type 1 diabetes

Monoclonal antibodies used for the treatment of cancer (checkpoint inhibitors inhibiting PD-1 and PD-L1), especially nivolumab and pembrolizumab have been reported to occasionally induce autoimmune diabetes. Diagnosis Diabetes is typically diagnosed by a blood test showing unusually high blood sugar. The World Health Organization defines diabetes as blood sugar levels at or above 7.0 mmol/L (126 mg/dL) after fasting for at least eight hours, or a glucose level at or above 11.1 mmol/L (200 mg/dL) two hours after an oral glucose tolerance test. The American Diabetes Association additionally recommends a diagnosis of diabetes for anyone with symptoms of hyperglycemia and blood sugar at any time at or above 11.1 mmol/L, or glycated hemoglobin (hemoglobin A1C) levels at or above 48 mmol/mol.

Atherosclerotic Risk Factors in Patients with Ischemic Cerebrovascular Disease.

Aggressive treatment of atherosclerotic risk factors can substantially reduce stroke risk in patients with a history of stroke or transient ischemic attack. Data from several recent large clinical trials provide convincing evidence of benefit for a number of specific therapies directed at this population. The authors recommend treatment with ramipril alone or perindopril plus indapamide regardless of blood pressure, provided there is no contraindication. For patients already taking a different angiotensin- converting enzyme (ACE) inhibitor, the authors do not routinely switch agents. The authors recommend use of simvastatin 40 mg per day in patients with a total cholesterol level of 135 mg/dL or greater, provided no contraindication exists. The authors also recommend consideration of gemfibrozil in patients with isolated low high- density lipoprotein levels. In patients with diabetes mellitus, tight glycemic control has not been shown to reduce macrovascular complications such as stroke, but does reduce microvascular complications. However, diabetics should receive especially aggressive treatment of other vascular risk factors. There is no role for post-menopausal hormone replacement therapy in prevention of stroke. Weight loss for overweight patients, regular exercise, and a diet rich in fruits, vegetables, cereals, and fish, as well as low in fat and cholesterol, should be a standard recommendation for this group of patients. Treatment with folic acid, B(6), and B(12) for patients with elevated homocysteine appears rational, though this is unproven. However, there is no benefit to vitamin E, vitamin C, or beta-carotene supplementation. Smokers should stop. For every 43 smokers who quit, one stroke is prevented. Moderate consumption of alcohol (one to two drinks a day) may be beneficial, but heavy alcohol use (more than five drinks a day) increases stroke risk.

Relative and cumulative effects of lipid and blood pressure control in the Stroke Prevention by Aggressive Reduction in Cholesterol Levels trial.

The relative contributions of on-treatment low- and high-density lipoprotein cholesterol (LDL-C, HDL-C), triglycerides, and blood pressure (BP) control on the risk of recurrent stroke or major cardiovascular events in patients with stroke is not well defined. We randomized 4731 patients with recent stroke or transient ischemic attack and no known coronary heart disease to atorvastatin 80 mg per day or placebo. After 4.9 years, at each level of LDL-C reduction, subjects with HDL-C value above the median or systolic BP below the median had greater reductions in stroke and major cardiovascular events and those with a reduction in triglycerides above the median or diastolic BP below the median showed similar trends. There were no statistical interactions between on-treatment LDL-C, HDL-C, triglycerides, and BP values. In a further exploratory analysis, optimal control was defined as LDL-C <70 mg per deciliter, HDL-C >50 mg per deciliter, triglycerides <150 mg per deciliter, and SBP/DBP <120/80 mm Hg. The risk of stroke decreased with as the level of control increased (hazard ratio [95% confidence interval] 0.98 [0.76 to 1.27], 0.78 [0.61 to 0.99], 0.62 [0.46 to 0.84], and 0.35 [0.13 to 0.96]) for those achieving optimal control of 1, 2, 3, or 4 factors as compared to none, respectively. Results were similar for major cardiovascular events. We found a cumulative effect of achieving optimal levels of LDL-C, HDL-C, triglycerides, and BP on the risk of recurrent stroke and major cardiovascular events. The protective effect of having a higher HDL-C was maintained at low levels of LDL-C.

The HOPE Study (Heart Outcomes Prevention Evaluation).

The Heart Outcomes Prevention Evaluation (HOPE) study was designed to test the hypotheses that two preventive intervention strategies, namely angiotensin-converting enzyme (ACE) inhibition or vitamin E, would improve morbidity and mortality in patients at high risk of cardiovascular events compared with placebo. This review addresses the ACE inhibitor (ACE-I) (ramipril) arm of the study, both on the trial population as a whole, and on the large diabetic subgroup. Patients were included in the study who were considered to be at high risk of future fatal or non-fatal cardiovascular events, by virtue of their age (>55 years), existing or previous cardiovascular disease, or diabetes. Diabetics had at least one other risk factor, either known vascular disease or other factors such as cigarette smoking, high cholesterol or hypertension. Ramipril or placebo was added to concomitant medication, which included, in a substantial proportion of patients, antihypertensive drugs (excluding ACE-I), lipid-lowering agents or aspirin. As a result, despite a history of hypertension in nearly 50% of patients, blood pressure (BP) at baseline was normal and the reduction in BP attributable to ramipril modest (a fall of 3-4 mmHg systolic BP and 1-2 mmHg diastolic). The trial was stopped early on the advice of the Data Monitoring Committee because of convincing evidence of the benefit of ramipril treatment on the combined primary endpoint of cardiovascular death, non-fatal myocardial infarct (MI) and non-fatal stroke (14% vs. 17.8% on ramipril and placebo, respectively; relative risk reduction 22%, p<0.001). This comprised a risk reduction of 32% for stroke, 20% for MI, 26% for cardiovascular death and 16% for all-cause mortality, as well as a reduction in the risk of several other endpoints including heart failure and revascularisation procedures. The results among the 3577 diabetic subjects were even more striking, with a reduction of 25% in the combined primary endpoint. This reduction in the combined endpoint and in particular the reduction in MI far exceeded that which would be expected from the modest fall in BP. Furthermore, a multiple regression analysis of the diabetic subgroup showed similar relative risk reductions even after allowing for the effects of the fall in BP. Possible explanations for the non BP-mediated benefits of ramipril include reduction of angiotensin II-induced intimal and vascular smooth muscle proliferation and possible plaque stabilisation. The HOPE study results show that it is both safe and beneficial to lower BP that is already within the 'normal' range, particularly in patients with known vascular risk factors. This should greatly extend the use of ACE-I to a wider group of patients - not only those with left ventricular dysfunction, hypertension or diabetic microalbuminuria, but to the sort of high-risk patients who are currently given prophylactic treatment with aspirin.

How to prevent and treat pharmacological hypoglycemias.

A 58 year-old woman with type 2 diabetes diagnosed 3 years before came to our clinic. Her treatment was metformin 850 mg every 12 hours and glimepiride 4 mg every 24 hours. After the initiation of glimepiride 9 months before her weight has increased 5 kg, and she suffers frequent hypoglycemias which have affected her while driving. Her BMI is 35.5 kg/m². She has a normal eye fund exam. She has hypertension treated with telmisartán and hidroclorotiazide with adequate control, and also hypercholesterolemia treated with atorvastatine 40 mg every 24 hours. Her blood test shows an HbA1c of 7.0%, normal values of microalbuminuria, total cholesterol 149 mg/dl, HDL cholesterol 52 mg/dl, LDL cholesterol 98 mg/dl and triglycerides 123 mg/dl. Her blood pressure is 129/81 mmHg, there was no orthostatic hypotension, and her peripheral neurological examination shows normal results. In summary, our case is a young woman with type 2 diabetes and obesity, without chronic complications and which has frequent hypoglycaemia. How must this woman be evaluated and treated?

Stroke prevention: management of modifiable vascular risk factors.

Stroke prevention is a crucial issue because (i) stroke is a frequent and severe disorder, and (ii) acute stroke therapies that are effective at the individual level have only a little impact in term of public health. Stroke prevention consists of the combination of 3 strategies: an optimal management of vascular risk factors, associated when appropriate with antithrombotic therapies, carotid surgery, or both. Primary prevention trials have shown that reducing blood pressure in hypertensive subjects reduces their vascular risk, including stroke. The association of perindopril plus indapamide reduces the vascular risk in patients who have had a stroke or TIA during the last 5 years, irrespective of their baseline blood pressure. Lowering serum cholesterol with statins or gemfibrozil in patients with hypercholesterolemia or coronary heart disease (CHD), reduces the risk of stroke. However, no trial of cholesterol-lowering therapy has been completed in stroke patients. A strict control of high cholesterol levels should be encouraged, because of benefits in terms of CHD. Statins should be prescribed for stroke patients with CHD, or increased cholesterol levels. Cigarette smoking is associated with an increased risk of stroke and should be avoided. Careful control of all risk factors, especially arterial hypertension in type 1 and type 2 diabetics is recommended, together with a strict glycemic control to reduce systemic microvascular complications. Estrogens prescribed in hormone replacement or oral contraceptive therapies are not recommended after an ischemic stroke. It is also recommended to reduce alcohol consumption and obesity, and to increase physical activity in patients at risk for first-ever or recurrent stroke. An optimal management of risk factors for stroke is crucial to reduce the risks of first-ever stroke, recurrent stroke, any vascular event after stroke and vascular death. One of the major public health issues for the coming years will be to focus more on risk factor recognition and management.

Type 2 diabetes

Management of type 2 diabetes focuses on lifestyle interventions, lowering other cardiovascular risk factors, and maintaining blood glucose levels in the normal range. Self-monitoring of blood glucose for people with newly diagnosed type 2 diabetes may be used in combination with education, although the benefit of self-monitoring in those not using multi-dose insulin is questionable. In those who do not want to measure blood levels, measuring urine levels may be done. Managing other cardiovascular risk factors, such as hypertension, high cholesterol, and microalbuminuria, improves a person's life expectancy. Decreasing the systolic blood pressure to less than 140 mmHg is associated with a lower risk of death and better outcomes. Intensive blood pressure management (less than 130/80 mmHg) as opposed to standard blood pressure management (less than 140-160 mmHg systolic to 85–100 mmHg diastolic) results in a slight decrease in stroke risk but no effect on overall risk of death.

Maintenance of Clinical Endpoints After Discharge from a Pharmacist-Managed Risk Reduction Clinic at a Veterans Affairs Medical Center.

Diabetes, dyslipidemia, and hypertension are complex chronic disease states that often require close monitoring and frequent follow-up to achieve and maintain therapeutic control as determined by hemoglobin A1c (A1c), low-density lipoprotein (LDL), and blood pressure (BP). At the Charles George Veterans Affairs Medical Center (CGVAMC), physicians may refer their patients to the on-site pharmacist-managed Risk Reduction Clinic (RRC). Patients are discharged from the RRC once patient-specific therapeutic goals have been met for diabetes, dyslipidemia, and/or hypertension. This study investigated the change in A1c, LDL, and systolic blood pressure (SBP) after discharge from the CGVAMC RRC. To investigate (a) how clinical endpoints for diabetes, dyslipidemia, and hypertension change after discharge from the pharmacist-managed RRC at the CGVAMC; (b) the factors associated with worsening of monitoring parameters; and (c) the frequency of reconsultation to the RRC. In this single-center retrospective quality management study, patients were included if they had a completed consultation to the CGVAMC RRC between August 11, 2008, and January 1, 2011, for the management of type 2 diabetes, dyslipidemia, and/or hypertension. Patients were included if they were discharged from the RRC prior to October 1, 2011, due to goal attainment. Furthermore, it was required that patients have A1c, LDL, and SBP measurements, as applicable based on diagnoses, at least yearly during the first 2 years following discharge. Patients were excluded if they were discharged for any reason other than goal attainment or if they were followed by a specialty clinic related to the RRC, including the Diabetes PharmD, Diabetes MD, MIDAS (group diabetes), or MAGIC (group dyslipidemia) clinics. Data collection included patient demographics; date of and indication for consultation to the RRC; date of first RRC visit; date of discharge from the RRC; number of visits to the RRC; A1c, LDL, SBP, and weight at consultation to the RRC, at discharge, and during the 2 years following discharge from the RRC; and date of and indication for reconsultation to the RRC, as applicable. Two-tailed paired t-tests were used to compare A1c, LDL, and SBP at discharge from the RRC to A1c, LDL, and SBP during the follow-up period. Two-tailed unpaired t-tests were performed to determine which variables were associated with changes in the monitoring parameters after discharge from the RRC. One hundred forty-nine patients were included in this study. For all patients with a diagnosis of diabetes (N = 82), A1c rose from 6.49% to 6.79% (P < 0.001) during the first year and to 7.04% (P < 0.001) during the second year following discharge. For patients diagnosed with dyslipidemia (N = 137), LDL rose after discharge from 81.5 mg/dL to 90.8 mg/dL (P < 0.001) and to 90.9 mg/dL (P < 0.001), respectively. For patients diagnosed with hypertension (N = 132), SBP rose from 126.2 mm Hg to 131.5 mm Hg (P < 0.001) and to 133.9 mm Hg (P < 0.001), respectively. An increase in A1c after discharge was associated with lower discharge A1c (P = 0.014), higher consultation weight (P = 0.009), and higher discharge weight (P = 0.042). A rise in LDL was correlated to higher consultation LDL (P = 0.006), while higher SBP was associated with lower discharge SBP (P < 0.001). Twelve percent of patients were reconsulted to the RRC. A1c, LDL, and SBP rose after discharge from the pharmacist-managed risk reduction clinic, but these changes may not have been clinically significant based on the low reconsultation rate and values remaining close to generally accepted therapeutic goals. Patients likely to benefit from extending RRC services past goal attainment include those with higher A1c and LDL at the time of consultation and those with higher weight. As a result of this study, recommendations have been made to consider following up every 3-4 months for 2-3 additional visits for patients with baseline A1c > 8% and LDL > 115 mg/dL and those with weight > 220 pounds prior to discharging them from the CGVAMC RRC. Furthermore, we believe that all patients could benefit from extending follow-up to 6 months for 1-2 additional visits or as needed after their therapeutic goals have been reached.

[Treatment of diabetes in metabolic syndrome].

Hyperglycaemia is a typical feature of metabolic syndrome (MeTS) and one of its independent diagnostic criteria. The term includes impaired glucose homeostasis (impaired fasting glucose and impaired glucose tolerance) and type 2 diabetes mellitus. Although glycaemic control has been shown to lower the risk of microvascular events, the effect of intensive glycaemic control on macrovascular outcomes is less clear. Epidemiological studies show hyperglycaemia, particularly the postprandial one, to be a clear risk factor for cardiovascular (CV) mortality and morbidity. However, the intervention studies are less conclusive. The large interventional studies published in 2008 and 2009 (UKPDS, VADT, ACCORD, ADVANCE, RECORD) advocate the controlling of nonglycemic risk factors (through blood pressure control, lipid lowering with statin therapy, aspirin therapy, and lifestyle modifications) as the primary strategies for reducing the burden of CV disease in people with diabetes, and demonstrated the need for individualized approach to the patients' care in terms of blood glucose control. The patients with shorter duration of type 2 diabetes and without established atherosclerosis might reap CV benefit from intensive glycemic control. Conversely, it is possible that potential risks of intensive glycaemic control (hypoglycaemia) may outweigh its benefits in other patients, such as those with a very long duration ofdiabetes, known history of severe hypoglycemia, advanced atherosclerosis, and advanced age/frailty. According to the latest recommendations of the Czech Diabetes Society that are in line with the European and US standards the best way to protect type 2 diabetic patients against coronary and cerebrovascular disease is to target all cardiovascular risk factors (blood pressure treatment, including lipid-lowering with statins, aspirin prophylaxis, smoking cessation, and healthy lifestyle behaviors hypertension, dyslipidemia, obesity and other symptoms of metabolic syndrome. The target HbA1c levels in patients with the low CV risk shoul be below 4.5%. Less strict goals (HbA1c below 6%) may be appropriate for patients with a history of severe hypoglycemia, limited life expectancy, advanced microvascular or macrovascular complications, or extensive comorbid conditions or those with long-standing diabetes. The individual targets should be achieved safely (without hypoglycaemias). Slow advancing in diabetes compensation is preferred. Lifestyle changes are the cornerstone of therapy. Metformin is the drug of choice; its administration, together with lifestyle changes, should be initiated immediately after the diagnoses of diabetes. If monotherapy does not provide satisfactory glucose control, other oral antidiabetic agents or insulin are added to the combination. Since it is not known which hypoglycaemic agents are beneficial from the perspective of long-term patient prognosis, the selection is liberal. Contraindication of the various farmaceuticals must be respected. It is possible to use a range of different combinations, metformin is administered with a glitazone (zero risk of hypoglycaemias is the advantage) with sulphonylurea derivatives (low price is the advantage) with glinides, with incretins, acarbose, antiobesity agents or insulin. The next step is a triple combination of hypoglycaemic agents with different mechanisms of action. Therapy also includes education focusing on changes to dietary and lifestyle habits, including smoking cessation, and education related to the prevention of complications, with particular regard to prevention of diabetic foot and atherosclerosis.

[The best of epidemiology and cardiovascular prevention in 2006].

The recent analysis of the French MONICA registries report a reduction in the incidence of fatal MI related to improvement of care whereas the overall incidence of coronary events remain stable, suggesting the need for a better primary prevention. The extensive review of the death certificates and the analysis of the death classification from the same registries indicate an under estimation of MI-related death in the national death registry. It is also confirmed that instead of 50%, approximately 80% of coronary death are explained by the four major risk factors including smoking, hypercholesterolemia, hypertension and diabetes. The international REACH registry has enrolled more than 67 000 individuals including patients with symptomatic atherothrombotic disease and patients with multiple risk factors. The analysis of baseline characteristics and of the one year FU shows a high residual risk and a lack of efficacy of secondary prevention. The existence of a symptomatic disease and the number of symptomatic localization of atherothrombosis are critical factors to predict recurrence of major vascular events Secondary analysis of the INTERHEART study provide the essence of what should any physician know about the relationship between coronary heart disease and smoking, either active or passive. Prevention with respect to this risk factor remains very insufficient. Varenicline, a new nicotinic receptor partial agonist, should help patients involved in smoking cessation program. The established detrimental effects of perioperative smoking represent a unique opportunity to promote smoking cessation in individuals scheduled for surgery. The major cardiovascular impact of second hand smoking has been recently demonstrated by the short-term effects of banning smoking in public places on the incidence of acute coronary events. The SPARCL study has demonstrated the benefit of high dose of atorvastatine to prevent recurrent acute ischemic cerebrovascular event in patients with a prior history of stroke or TIA. In the open ASTEROID study, high doses of rosuvastatine confirm the possibility of reducing the volume of coronary atheroma analyzed by IVUS. The expected benefit of glitazones to reduce the incidence of death, MI and stroke in diabetes patients with a prior history of vascular event has been confirmed in the PROactive study. Pioglitazone provided a clear reduction of recurrent vascular events in diabetes patient with a prior MI at a cost of a significant increase of the risk of heart failure. In the DREAM study, neither ramipril nor rosiglitazone have reduced the incidence of cardiovascular events significantly. The moderate benefit of the fenofibrate to prevent cardiovascular events in the FIELD study, which was carried out in diabetics mostly in primary prevention, needs to be considered after adjustment on statin use in a higher proportion of patients of the placebo group. Postprandial hyperglycaemia, analyzed by the peak of glycaemia after a load in glucose, has been confirmed as a more powerful independent predictive factor of the risk of cardiovascular event than fasting glycaemia. The systematic screening postprandial hyperglycaemia represents an interesting strategy for primary prevention which warrants further investigation. If obesity is a risk factor whose impact on morbi-mortality is well established, a French study shows that body mass index has an unfavourable influence on the cognitive functions in middle-aged men and women.