Insulin

Renal Potassium Reabsorption and Secretion

July 24, 2016 Cardiology, Critical Care, Nephrology, Physiology and Pathophysiology No comments , , , , , , , , , , ,

Percentage of fitered load transported at different locations depending on diet

Screen Shot 2016-07-31 at 5.02.46 PM

The Importance of Potassium Balance

The vast majority of body potassium is freely dissolved in the cytosol of tissue cells and constitutes the major osmotic component of the intracellular fluid (ICF). Only about 2% of total-body potassium is in the extracellular fluid (ECF). This small fraction, however, is absolutely crucial for body function, and the concentration of potassium in the ECF is a closely regulated quantitiy. Major increases and decreases (called hyperkalemia and hypokalemia) in plasma values are cause for medical intervention. The importance of maintaining this concentration stems primarily from the role of potassium in the excitability of nerve and muscle, especially the heart.

The ratio of the intracellular to extracellular concentration of potassium is the major determinant of the resting membrane potential in these cells. A significant rise in the extracellular potassium concentration causes a sustained depolarization. Low extracellular potassium may hyperpolarize or depolarize depending on how changes in extracellular potassium affect membrane permeability. Both conditions lead to muscle and cardiac disturbances.


Potassium Movement Between the ICF and ECF

Given that the vast majority of body potassium is contained within cells, the extracellular potassium concentration is cruically dependent on 1).the total amount of potassium in the body and 2).the distribution of this potassium between the extracellular and intracellular fluid compartments. Total-body potassium is determined by the balance between potassium intake and excretion. Healthy individuals remain in potassium balance, as they do in sodium balance, by excreting potassium in response to dietary loads and withholdin g excretion when body potassium is depleted. The urine is the major route of potassium excretion, although some is lost in the feces and sweat. Normally the losses via sweat and the gastrointestinal tract are small, but large quantities can be the lost from digestive tract during vomiting or diarrhea. The control of renal potassium transport is the major mechanism by which total-body potassium is maintained in balance.

The high level of potassium within cells is maintained by the collective operation of the Na-K-ATPase plasma membrane pumps, which actively transport potassium into cells. Because the total amount of potassium in the extracellular compartment is so small (40-60 mEq total), even very slight shifts of potassium into or out of cells produce large changes in extracellular potassium concentration. Similarly, a meal rich in potassium (e.g., steak, potato, and spinach) could easily double the extracellular concentration of potassium if most of that potassium were not transferred from the blood to the intracellular compartment. It is crucial, therefore, that dietary loads be taken up into the intracellular compartment rapidly to prevent major changes in plasma potassium concentration.

The tissue contributing most to the sequestration of potassium is skeletal muscle, simply because muscle cells collectively contain the largest intracellular volume. Muscle effectively buffers extracellular potassium by taking up or releasing it to keep the plasma potassium concentration close to normal. On a moment-to-moment basis, this is what protects the ECF from large swings in potassium concentration. Major factors involved in these homeostatic processes include insulin and epinephrine, both of which cause increased potassium uptake by muscle and certain other cells through stimulation of plasma membrane Na-K-ATPases. Another influence is the gastrointestinal tract, which contains an elaborate neural network (the "gut brain") that sends signals to the central nervous system. It also contains a complement of enteroendocrine cells that release an array of peptide hormones. Together these neural and hormonal signals affect many target organs, including the kidneys in response to dietary input.

The increase in plasma insulin concentration after a meal is a crucial factor in moving potassium absorbed from the GI tract into cells rather than allowing to accumulate in the ECF. This newly ingested potassium then slowly comes out of cells between meals to be excreted in the urine. Moreover, a large increase in plasma potassium concentration facilitates insulin secretion at any time, and the additional insulin induces greater potassium uptake by the cells.

The effect of epinephrine on cellular potassium uptake is probably of greatest physiological importance during exercise when potassium moves out of muscle cells that are rapidly firing action potentials. In fact, very intense intermittent exercises such as wind sprints can actually double plasma potassium for a brief period. However, at the same time, exercise increases adrenal secretion of epinephrine, which stimulates potassium uptake bu the Na-K-ATPase in muscle and other cells and transiently high potassium levels are restored to normal with a few minutes of rest. Similarly, trauma causes of loss of potassium from damaged cells and epinephrine released due to stress stimulates other cells to take up plasma potassium.

Another influence on the distribution of potassium between the ICF and ECF is the ECF hydrogen ion concentration: An increase in ECF hydrogen ion concentration is often associated with net potassium movement out of cells, whereas a decrease in ECF hydrogen ion concentration causes net potassium movement into them. It is as though potassium and hydrogen ions were exchanging across plasma membranes.


Renal Potassium Handling

Althgouh skeletal msucle and other tissues play an important role in the moment-to-moment control of plasma potassium concentration, in the final analysis, the kidney determines total-body potassium content. It is helpful to keep in mind several major differences between teh renal handling of sodium and potassium.

  • The filtered load of sodium is 30 to 40 times greater than the filtered load of potassium and the tubules always have to recover the majority of filtered sodium. This is not the case for potassium.
  • Sodium is only reabsorbed, never sereted. In contrast, potassium is both reabsorbed and secreted, ant its regulation is primarily focused on secretion.
  • The renal handling of sodium has a much greater effect on potassium than vice versa, which is a major feature of control.

Potassium is freely filtered into Bowman's space. Under all conditions, almost all the filtered load (~90%) is reabsorbed by the proximal tubule and thick ascending limb of the loop of Henle. Then, if the body is conserving potassium, most of the rest is reabsorbed in the distal nephron and medullary collecting ducts, leaving almost none in the urine. In contrast, if the body is ridding itself of potassium, a large amount is secreted in the distal nephron, resulting in a substantial excretion, of which the amount excreted may exceed the filtered load when secretion occurs at high rates.

PS: Proximal tubule reabsorption percentage: 65%; thick ascending limb of the loop of Henle reabsorption percentage: 25%

Proximal tubule

In the proximal tubule about 65% of the filtered load is reabsorbed, mostly via the paracellular route. The flux is driven by the concentration gradient set up when water is reabsorbed, which concentrates potassium and other solutes remaining in the tubular lumen. This flux is essentially unregulated and varies mostly with how much sodium, and therefore water, is reabsorbed.

The active transport of potassium is always coupled to the active transport of another solute, either sodium or hydrogen. In the proximal tubule the efflux of sodium by the Na-K-ATPase is very vigorous, requiring a high rate of potassium uptake from the interstitium. Since we know that there is net potassium transport into the interstitium, this pumped potassium must therefore recycle right back by passive flux through channels in the basolateral membrane. In some regions influx of potassium across apical membranes occurs via H-K antiporters that are simultaneously secreting protons.

The loop of Henle

The loop of Henle continues the reabsorption of potassium. The major events take place in the thick ascending limb, where the Na-K-2Cl multiporter in the apical membrane of the tubular cells takes up potassium. The interaction with sodium in these cells is even more complicated than in the proximal tubule because potassium is transported into the bubular cells both from the lumen with sodium via Na-K-2Cl symporters and from the interstitium via the Na-K-ATPase. The tubule contains far less potassium than sodium, but the Na-K-2Cl transporter moves equal amounts of each one. Therefore to supply enough potassium to accompany the large amount of sodium being reabsorbed by the symporter, potassium must recycle back to the lumen by passive channel flux. If this did not happen then sodium reabsorption would be limited only to the amount of potassium present in the tubular fluid.

Some potassium entering from the lumen does move through the cells and exit across the basolateral membrane along with the potassium entering via the Na-K-ATPase. It exits by a combination of passive flux through channels and through K-Cl symporters with chloride, thus yielding net transcellular reabsorption. Some potassium is also reabsorbed by the paracellular route in this segment, driven by a lumen-positive voltage.

The distal nephron

The distal convoluted tubule and connecting tubule stand out as being particularly imporant in potassium handling because of their rich complement of transport elements and their location prior to segments where most of water is absorbed. These regions play a major role in potassium secretion when total body potassium is high (high potassium diet). The distal nephron expresses both reabsorptive and secretory mechanisms, and it is the quantitative amount of each that determines net potassium excretion. There are several cell types in the epithelium of the connecting tubule and cortical collecting duct. Principal cells (approximately 70% of the cells) and intercalated cells. The intercalcated cells are further subdivided into type A (more numerous), type B (sparse) and a third type called non-A non-B cells. Potassium secretion occurs in principal cells, whereas the type A intercalated cells reabsorb potassium. The mechanisms of both secretion and reabsorption are straightforward. Secretion of potassium by principal cells involves the uptake of potassium from the interstitium via the Na-K-ATPase and secretion into the tubular lumen through channels. Type A intercalated cells reabsorb potassium via the H-K-ATPase in the apical membrane, which actively takes up potassium from the lumen. They then allow potassium to enter the interstitium across the basolateral membrane via potassium channels.

Finally, the medullary collecting ducts reabsorb small amounts of potassium under all conditions. When the sum of upstream processes has already reabsorbed almost all the potassium, the medullary collecting ducts bring the final urine excretion down to a few percent of the filtered load, for an excretion of about 10 to 15 mEq/day. On the other hand, if upstream segments are secreting avidly, the modest reabsorption in the medullary collecting ducts does little to prevent an excretion that can reach 1000 mEq/day.


Regulation of Potassium Excretion

The mechanisms regulating potassium excretion are as complex, and perhaps more so, than those regulating sodium excretion. And as pointed out earlier, active potassium trasnport is intertwined with sodium and hydrogen transport. But within the complexity one thing is abundantly clear – the healthy kidneys do a remarkable job of integrating signals to increase potassium excretion in response to high dietary loads and reduce excretion in the face of restricted diets.

The key regulated variable is potassium secretion by principal cells in the distal nephron. There are 3 transport processes in these cells that determine the amount of secretion: potassium influx by the Na-K-ATPase, potassium efflux into the lumen, and potassium efflux back into the interstitium (recycling). Much of the control is exerted on the activity of potassium channels. The kidneys and other body organs express numerous potassium channel species; for simplicity we do not usually differentiate between types. However in the apical membrane of principal cells in the distal nephrone, 2 types of channels stand out as being those that secrete potassium in a regulated manner: ROMK and BK. Although ROMK and BK channels are both permeable to potassium, they play different mechanisms. At very low dietary loads of potassium, there is virtually no secretion by either kind of channel. ROMK channels are sequestered in intracellular vesicles and BK channels are closed. At normal potassium loads, ROMK channels are moved to the apical membrane and secrete potassium at a modest rate. BK channels are still closed, held in reserve and ready to respond to appropriate signals when needed. At high excretion rates, both types of channel are present in the luminal membrane and avidly secreting potassium being pumped in by the Na-K-ATPase.

Plasma potassium

First, the filtered load is directly proportional to plasma concentration. Second, the environment of the principal cells that secrete potassium, that is, the cortical interstitium, has a potassium concentration that is nearly the same as in plasma. The Na-K-ATPase that takes up potassium is highly sensitive to the potassium concentration in this space, and varies its pump rate up and down when potassium levels in the plasma vary up and down. Thus plasma potassium concentration exerts an influence on potassium excretion, but is not the dominant factor under normal conditions.

Dietary potassium

Dietary potassium must be matched by renal excretion. The healthy kidneys do this very well by increasing and decreasing potassium excretion in parallel with dietary load. Just how the kidneys "know" about dietary input is still somewhat mysterious. Although very large potassium loads can increase plasma potassium somewhat, the changes in excretion assocaited wtih ordinary fluctuations in dietary input do not seem to be accounted for on the basis of either changes in plasma potassium or the other identified factors. One factor known to exert an influence, but not the major one, is the previously mentioned gastrointestinal peptide hormones released in response to ingested potassium. They influence not only the cellular uptake of potassium absorbed from the GI tract, but also the renal handling ot potassium, and seem to be one of the links between dietary load and excretion.

A manifestation of changing dietary loads over time is to regulate the distribution of ROMK channels between the apical membrane and intracellular storage, that is, high-potassium diets lead to insertion of apical channels and therefore highest potassium secretion. In contrast, during periods of prolonged low potassium ingestion, there are few ROMK channels in the apical membrane. Yet another adaptation to prolonged periods of low potassium ingestion is an increase in H-K-ATPase activity in intercalated cells, resulting in even more efficient reabsortpion of filtered potassium.

Aldosterone

A stimulator of aldosterone secretion by the adrenal cortex, in addition to AII, is an increase in plasma potassium concentration. This is a direct action of potassium and does not involve the renin-angiotensin system. If anything, high levels of potassium decrease the formation of AII. Aldosterone, as well as increasing expression of the Na-K-ATPase and ENaC sodium channels, also stimulates the activity of ROMK channels in principal cells of the distal nephron. Both actions have the effect of increasing potassium secretion. Greater pumping by the Na-K-ATPase supplies more potassium from the interstitium to the cytosol of the principal cells, and more functioning ROMK channels provide more pathways for secretion. Conversely, low levels of aldosterone deter potassium secretion.

Angiotensin II

AII is an inhibitor of potassium secretion. Its mechanism of action is to decrease the activity of ROMK channels in principal cells and distal convoluted cells, thereby limiting the potassium flux from cell to lumen. Thus AII and aldosterone exert influences on potassium excretion in opposite directions.

Delivery of sodium to principal cells

Sodium delivery to principal cells in the connecting tubule and cortical collecting duct is a major regulator. High sodium delivery stimulates potassium secretion. It does so in 2 ways. First, sodium entry via sodium channels (ENaC?) in principal cells depolarizes the apical membrane and thereby increases the electrochemical gradient driving the outward flow of potassium through channels. Second, more sodium delivered means more sodium taken up, and therefore more sodium pumped out by the Na-K-ATPase, in turn causing more potassium to be pumped in. Sodium delivery to principal cells, and hence potassium secretion, is strongly affected by the amount of sodium reabsorption in prior segments.

The Management of Hyperglycemic Crises in Diabetes

November 11, 2013 Critical Care, Diabetes, Pharmacotherapy, Therapeutics No comments , , , ,

Diabetic ketoacidosis (DKA) and the hyperosmolar hyperglycemic state (HHS) are the two most serious acute metabolic complications of diabetes. The triad of uncontrolled hyperglycemia, metabolic acidosis (SAG elevated metabolic acidosis), and increased total body ketone concentration characterizes DKA. HHS is characterized by severe hyperglycemia, hyperosmolality, and dehydration in the absence of significant ketoacidosis.

Pathogenesis

DKA

In DKA, hyperglycemia develops as a result of three processes: increased gluconeogenesis, accelerated glycogenolysis, and imaired glucose utilization by peripheral tissues.

The mechanisms of these three processes include: reduced effective insulin concentrations and increased concentrations of counterregulatory hormones (catecholamines, cortisol, glucagon, and growth hormone) lead to hyperglycemia and ketosis.

The combination of insulin deficiency and increased counterregulatory hormones in DKA lead to the release of free fatty acids into the circulation from adipose tissue (lipolysis) and to unrestrained hepatic fatty acid oxidation in the liver to ketone bodies (β-hydroxybutyrate and acetoacetate), with resulting ketonemia and metabolic acidosis.

HHS

The pathogenesis of HHS is not as well understood as that of DKA, but a greater degree of dehydration (due to osmotic diuresis) and differences in insulin availability distinguish it from DKA. Although relative insulin deficiency is clearly present in HHS, endogenous insulin secretion (reflected by C-peptide levels) appears to be greater than in DKA, where it is negligible. Insulin levels in HHS are inadequate to facilitate glucose utilization by insulin-sensitive tissues but adequate to prevent lipolysis and subsequent ketogenesis.

Figure 1. Pathogenesis of DKA and HHS

Precipitating Factors

The most common precipitating factor in the developmemt of DKA and HHS is infection. Other precipitating factors include discontinuation of or inadequate insulin therapy, pancreatitis, myocardial infarction, cerebrovascular accident, and drugs.

However, an increasing number of DKA cases without precipitating cause have been reported in patients with diabetes.

On admission, leukocytosis with cell counts in the 10,000-15,000 mm3 range is the rule in DKA and may not be indicative of an infectious process. However, leukocytosis with cell counts >25,000 mm3 may designate infection and require further evaluation.

Diagnosis

The key diagnostic feature in DKA is the elevation in circulating total blood ketone concentration and hyperglycemia. If available, measurement of β-hydroxybutyrate may be useful for diagnosis. For hyperglycemia, however, a wide range of plasma glucose can be present on admission.

While HHS is characterized by severe hyperglycemia, hyperosmolality, and dehydration in the absence of significant ketoacidosis. Studies on serum osmolality and mental alteration have established a positive linear relationship between osmolality and mental obtundation. The occurrence of stupor or coma in a diabetic patient in the absence of definitive elevation of effective osmolality (≥320 mOsm/kg) demands immediate consideration of other causes of mental status change.

PS: The effective osmolality can be calculated as: [sodium ion (mEq/L) × 2 + glucose (mg/dL)/18]. For example, a given serum sodium ion concentration of 100 mEq/L, with a serum glucose concentration of 750 mg/dL, the effective osmolality should be [100 × 2 + 750/18] = 241.67 mOsm/kg. Note that the BUN/urea concentration is not taken into account becaue it is freely permeable and its accumulation dose not induce major changes in intracellular volume or osmotic gradient across the cell membrane.

Diagnostic Criteria for DKA and HHS

Treatment

Fluid and Electrolyte Correction

Successful treatment of DKA and HHS requires correction of dehydration, hyperglycemia, and electrolyte imbalances; identification of comorbid precipitating events; and above all, frequent patient monitoring. Generally, the treatment strategies include fluid therapy (necessary), insulin therapy (necessary), potassium correction (necessary), pH correction (if necessary), and phosphate correction (if necessary).

Initial fluid therapy for both DKA and HHS is fluid replacement with 0.9% NaCl infused at a rate of 15-20 ml · kg body wt-1 · h-1 or  1-1.5 l during the first hour. Thereafter if the corrected serum sodium is low, 0.9% NaCl should be administered at a rate of 250-500 ml/h. Conversely, if the corrected serum after the fluid replacement of the initial first hour is normal or elevated, 0.45% NaCl infused at a rate of 250-500 ml/h is the strategy. Subsequent choice for fluid replacement depends on hemodynamics, the state of hydration, serum electrolyte levels, and urinary output.

Once the plasma glucose is ~ 200 mg/dL (DKA) or ~ 300 mg/dL (HHS), the fluid replacement should be changed to 5% dextrose with 0.45% NaCl at the drip rate of 150-250 ml/hr.

Despite total-body potassium depletion, mild-to-moderate hyperkalemia is common in patients with hyperglycemic crises. Insuilin therapy, correction of acidosis (alkali replacement enhance the risk of increased potassium waste), and volume expansion decrease serum potassium concentration. To prevent hypokalemia, potassium replacement is initiated after serum levels fall below the upper level of normal for the particular laboratory (5.0-5.2 mEq/L). The treatment goal of potassium replacement is to maintain srum potassium levels within the normal range of 4-5 mEq/L. Generally, 20-30 mEq potassium in each liter of infusion fluid is sufficient to get this goal. Rarely, DKA patients may present with significant hypokalemia. In such cases, potassium replacement should begin with fluid therapy (note that in such cases insulin therapy should be delayed until serum potassium restores to >3.3 mEq/Ll).

Despite whole-body phosphate deficits in DKA, serum phosphate is often normal or increased at presentation. Phosphate concentration decreases with inslulin therapy. However, prospective randomized studies have failed to show any beneficial effect of phosphate replacement on the clinical outcome in DKA, and overzealous phosphate therapy can cause severe hypocalcemia. But, to avoid potential cardiac and skeletal muscle weakness and respiratory depression due to hypophosphatemia, careful phosphate replacement may sometimes be indicated in patients with cardiac dysfunction and in those with serum phosphate concentration <1.0 mg/dL. When needed, 20-30 mEq/L potassium phosphate can be added to replacement fluids. For HHS, no studies are available on the use of phosphate.

The maximal rate of phosphate replacement generally regarded as safe to treat severe hypophosphatemia is 4.5 mmol/h.

Insulin Therapy

Low-dose regular insulin by intravenous infusion have demonstrated it effectiveness and benefit in the treatment of both DKA and HHS. Regular insulin should be given to patients with DKA or HHS on admission, but, for patients with significant hypokalemia on admission, insulin treatment should be delayed until patassium concentration is restored to >3.3 mEq/L. Regular insulin should be administered intravenously at a continuous dose of 0.1 U/kg/hr, with a prior IV bolus dose of 0.1 U/kg. If serum glucose dose not fall by at leaset 10% in the first hour, we should give 0.14 U/kg as IV bolus, then continue previous Rx.

Once the plasma glucose is ~ 200 mg/dL (DKA) or ~ 300 mg/dL (HHS), the rate of intravenously continuous regular insulin should be decreased to 0.02-0.05 U/kg/hr. Thereafter, the rate of insulin administration or the concentration of dextrose may need to be adjusted to maintain glucose values between 150 and 200 mg/dL in DKA or 250 and 300 mg/dL in HHS until they are resolved.

Transition to subcutaneous insulin. Once DKA or HHS is resolved, subcutaneous insulin theray can be started and continuous intravenous insulin should be allow a overlap of 1-2 h before discontinuation due to prevention recurrence of hyperglycemia or ketoacidosis during the transition period from IV insulin to SC insulin. Patients with known diabetes may be given insulin at the dosage they were receiving before the onset of DKA so long as it was controlling glucose properly. In insulin-naïve patients, a multidose insulin regimen should be started at a dose of 0.5-0.8 units · kg-1 · day-1.

Acid-Base Disorders

Prospective randomized study failed to show either beneficial or deleterious changes in morbidity or mortality with bicarbonate therapy in DKA patients with an admission arterial pH between 6.9 and 7.1. Nine small studies in a total of 434 patients with diabetic ketoacidosis (217 treated with bicarbonate and 178 without alkali therapy) support the notion that bicarbonate therapy for DKA offers no advantage in improving cardiac or neurologic functions or in the rate of recovery of hyperglycemia and ketoacidosis. However, due to the reason that severe acidosis may lead to a numerous adverse vascular effects, it is recommended that adult patients with a pH <6.9 should receive 100 mmol sodium bicarbonate in 400mml sterile water (an isotonic solution) with 20 mEq KCl (due to that alkali therapy enhance the risk of increased potassium wasting) administered at a rate of 200 ml/h for 2 hours until the venous pH is >7.0. If the pH is still <7.0 after this is infused, it is recommended repeating infusion every 2 h unitl pH reaches >7.0.

Recovery criteria

Criteria for resolution of ketoacidosis include a blood glucose <200 mg/dL and two of the following criteria: a serum bicarbonate level ≥15 mEq/L, a venous pH >7.3, and a calculated anion gap ≤12 mEq/L (DKA belongs to elevated anion gap metabolic acidosis).

Criteria for resolution of HHS is associated with normal osmolality and regain of normal mental status.

Use insulin Earlier, not Later, in type 2 diabetes

July 12, 2012 Diabetes, Therapeutics No comments ,

March 29, 2012 (New Orleans, Louisiana) — Insulin administration has traditionally been one of the last steps in the treatment of type 2 diabetes mellitus (T2DM), but that’s changing, says Jonathan Marquess, PharmD, from the Institute for Wellness and Education Inc in Atlanta, Georgia. He discussed the benefits of early initiation and intensification of insulin therapy in patients with T2DM at APhA 2012: American Pharmacists Association Annual Meeting and Exposition here.

Dr. Marquess spoke with Medscape Medical News about the benefits of early insulin initiation and about strategies for working with patients with T2DM.

Medscape: Would you describe early initiation and intensification of insulin therapy in patients with type 2 diabetes mellitus?

Dr. Marquess: It means utilizing the guidelines from the American Diabetes Association (ADA) and utilizing insulin sooner rather than later. All too often, physicians, nurses, and pharmacists, will advise patients to take oral agent #1, then oral agent #2, then oral agent #3, and then say, “Wow, I guess it’s time to start insulin.” Whereas, the data would show us that we ought to be starting insulin a little bit sooner, rather than utilizing all these oral agents.

Medscape: Why is this topic important?

Dr. Marquess: It gets back to the control. We have got a failing grade on the number of patients that have their diabetes in control. It is getting better, and I personally feel one of many reasons for this is that pharmacists are getting involved in diabetes management and medication therapy management.

There’s also an economic issue involved. In a lot of patients, the hemoglobin A1c is above 7%. The A1c should be 7%, according to the ADA. We know that diabetic complications happen at a more prevalent rate when the A1c is above 7. Those diabetic complications are where we’re really spending big, big money in this disease state.

Medscape: What have researchers learned most recently about the benefits of early initiation and intensification of insulin therapy in these patients?

Dr. Marquess: The proportion of patients with diabetes achieving [A1c levels] less than 7% is around 56% or 57%. The lower the A1c, the more important postprandial glucose levels are, so that’s why you also need to be checking their glucose.

You need to be looking at their numbers. Not only if the glucose level is right in the morning, but also 2 hours after a meal, and that’s when you have to also start thinking about using mealtime insulin.

Also, this is not data that’s just been published, but it’s very important data, in my opinion. It’s from the United Kingdom Prospective Diabetes Study, that says a 1% A1c decrease really reduces the risk of complications.

Medscape: How is insulin currently being used in patients with type 2 diabetes?

Dr. Marquess: We have great medications, excellent medications, and we have some fantastic insulins now that we didn’t have available just a few years ago. We can now match patients’ physiologic problems with the insulins. If they need a long-acting basal because their fasting plasma glucose levels are out of control, we’ve got some great basal insulins. If they need a very rapid-acting mealtime insulin, we’ve got 3 of those available now that are very, very good.

Medscape: What are some common misperceptions about the use of insulin in patients with type 2 diabetes?

Dr. Marquess: A big misperception is patients think the needle is really, really long. Some patients are scared of needles. Patients think they will be perceived as having bad control of their diabetes, or that they’ve done something wrong as a patient, but that’s not true at all. That’s a common perceived barrier. Some people say insulin is inconvenient to use. I think sometimes there is a fear of hypoglycemia, too.

Medscape: How do you deal with patients who are afraid of needles?

Dr. Marquess: I always say, “Let’s talk about insulin pens.” Make sure the patient is using insulin pens whenever possible, because they’re easy to learn, they’re easy to teach, there are fewer medication and dosing errors, and in my opinion, there’s better accuracy. Insulin pens can also usually overcome issues patients may have with dexterity.

Medscape: What are some of the challenges associated with educating patients with type 2 diabetes and ways of handling those challenges?

Dr. Marquess: One of the big challenges is that this is not a 10 second, “how to use your inhaler” talk. This disease is very complex, so it takes a little while, because you have to talk to them about things like watching what they’re eating. You have to talk to them about blood glucose monitoring, perhaps how to use a new glucose meter and what those numbers actually mean.

You have to talk to them about physical activity and how important that is, and how if they do get some physical activity, how their blood glucose might drop, and how to treat hypoglycemia with 15 grams of carbohydrate.

It’s a multifaceted disease. It’s also a progressive disease. It’s not like you can educate patients for 5 or 10 minutes, and not ever have to go back and talk to them about their disease again. It’s something you have to continually talk about, and you have to continually ask the patient how they’re doing.

Medscape: Is there anything else you’d like pharmacists to know about this topic?

Dr. Marquess: There’s no doubt that there’s an epidemic of diabetes. We have some 26 million people with diabetes, and the numbers keep going up. Complications are happening at a rapid rate. The positive thing is that it’s a disease that can be managed, if patients can get to know their pharmacist, and if pharmacists will utilize their great skills.

Dr. Marquess has disclosed no relevant financial relationships.

APhA 2012: American Pharmacists Association Annual Meeting and Exposition. Presented March 12, 2012.