Monthly Archives: February 2010

February 7, 2010 · 2:00 AM

Drug Review: Alpha-Glucosidase Inhibitors (acarbose and miglitol)

acarbose and miglitol for type 2 diabetesAlpha-glucosidase inhibitors (AGIs) available in the U.S. are acarbose (Precose) and miglitol (Glyset).  Drug names vary by country and manufacturer. 

This is only a brief review: consult your physician or pharmacist for full details.

How do they work?

Many of the carbohydrates we eat are just basic sugar molecules joined to each other by chemical bonds, creating disaccherides, oligosaccharides, and polysaccharides.  This is as true for bread and potatoes as it is for table sugar.  To digest and absorb them, we have to break them down into the basic sugar molecules (monosaccharides).  AGIs inhibit this breakdown process inside our intestine, decreasing the rise in blood sugar after we eat complex carbohydrates.  They delay glucose absorption.  So AGIs mainly decrease after-meal glucose levels.     

Uses

They work alone or in combination with other diabetic medications, especially if the diet contains over 50% of energy in the form of complex carbohydrates.  They are FDA-approved only for use in type 2 diabetes, but they have also been used in type 1. 

Dosing

The starting dose is the same for both:  25 mg by mouth three times daily with the first bite of each main meal.

Side effects

Belly pain, intestinal gas, diarrhea.  Slight risk of hypoglycemia when its used alone; higher risk when used with insulin shots or insulin secretagogues.  If hypoglycemia occurs, you have to eat glucose to counteract it, not your usual non-glucose items because you won’t absorb them properly.   

Don’t use if you have . . .

. . . Liver cirrhosis (refers to acarbose: miglitol can be used), kidney impairment, or intestinal problems.

Steve Parker, M.D.

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February 6, 2010 · 2:00 AM

What Is Normal Blood Sugar?

Lately I’ve been thinking about which carbohydrates might be added to the Ketogenic Mediterranean Diet to make it healthier yet remain diabetic-friendly.  Carbohydrates—some more than others—tend to elevate blood sugars in diabetics.  If I’m going to recommend adding carbs to the KMD, I have to give some idea what an acceptable blood sugar response would be.  An excessive rise in blood sugar level would necessitate eliminating that carbohydrate, reducing the serving size, or changing the diabetic medication regimen (increase a dose or add a new drug?) 

First off, I’ve reviewed what constitutes blood sugar levels in healthy non-diabetics before and after meals.  Those levels might give us some idea what to shoot for in diabetics. 

The following numbers refer to average blood sugar (glucose) levels in venous plasma, as measured in a lab.  Portable home glucose meters measure sugar in capillary whole blood.  Many, but not all, meters in 2010 are calibrated to compare directly to venous plasma levels.

Fasting blood sugar after a night of sleep and before breakfast: 85 mg/dl (4.72 mmol/l)

One hour after a meal: 110 mg/dl (6.11 mmol/l)

Two hours after a meal: 95 mg/dl (5.28 mmol/l)

Five hours after a meal: 85 (4.72 mmol/l)

(The aforementioned meal derives 50–55% of its energy from carbohydrate)

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Ranges of blood sugar for young healthy non-diabetic adults:

Fasting blood sugar: 70–90 mg/dl (3.89–5.00 mmol/l)

One hour after a typical meal: 90–125 mg/dl (5.00–6.94 mmol/l)

Two hours after a typical meal: 90–110 mg/dl (5.00–6.11 mmol/l)

Five hours after a typical meal: 70–90 mg/dl (3.89–5.00 mmol/l)

♦   ♦   ♦

Another way to consider normal blood sugar levels is to look at a blood test called hemoglobin A1c, which is an indicator of average blood sugar readings over the prior three months.  The average healthy non-diabetic adult hemoglobin A1c is 5% and translates into an average blood sugar of 100 mg/dl (5.56 mmol/l).  This will vary a bit from lab to lab.  Most healthy non-diabetics would be under 5.7%.

What Level of Blood Sugar Defines Diabetes and Prediabetes?  

According to the 2007 guidelines issued by the American Association of Clinical Endocrinologists:

Prediabetes (or impaired fasting glucose): fasting blood sugar 100–125 mg/dl (5.56–6.94 mmol/l)

Prediabetes (or impaired glucose tolerance): blood sugar 140–199 mg/dl (7.78–11.06 mmol/l) two hours after ingesting 75 grams of glucose

Diabetes: blood sugar 200 mg/dl (11.11 mmol/l) or greater two hours after ingesting 75 grams of glucose

Diabetes: random blood sugar 200 mg/dl (11.11 mmol/l) or greater, plus symptoms of diabetes

For my current thoughts on blood sugar goals for diabetics and prediabetics, please see the bottom half  of my “What is Normal Blood Sugar” page.

Steve Parker, M.D.

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February 5, 2010 · 2:00 AM

Drug Review: Thiazolidinediones (pioglitazone, rosiglitazone)

pioglitazone and rosiglitazone for type 2 diabetesThiazolidinediones are more easily referred to as TZDs or glitazones.  Compared to the usual first-choice drug for type 2 diabetes (metformin), the TZDs are significantly more expensive.

Remember that drug names—both generic and brand—may vary depending on country and manufacturer.  In the U.S., rosiglitazone is sold as Avandia; pioglitazone is Actos. This is just a brief overview: consult your physician or pharmacist for full details.

How do they work?

In short, TZDs increase glucose utilization  and decrease glucose production, leading to lower blood sugar levels.  They sensitize several tissues to the effect of insulin.  Insulin, among other actions, helps put circulating blood sugar into our muscles, fat cells, and (to a lesser extent) liver cells.  So blood sugar levels fall.  Thiazolidinediones (aka TZDs) make these tissues more sensitive to this effect of insulin.  Insulin also suppresses glucose production by the liver, an effect enhanced by TZDs.  They reduce insulin resistance.

TZDs may also help preserve pancreas beta cell function.  Beta cells produce insulin.

They reduce both fasting and after-meal glucose levels.  Fasting blood sugar drops and average of 40 mg/dl.  Hemoglobin A1c falls by 1 to 1.5% (absolute, not relative).

TZDs tend to improve blood lipids: lower triglycerides, higher HDL cholesterol, decreased small, dense LDL cholesterol.  Pioglitazone has the more pronouned effect.

On a cellular level, they activate peroxisome proliferator-activated receptor-gamma, so they are sometimes referred to as PPAR-gamma agonists.  Pioglitazone also affects PPAR-alpha.

Uses

TZDs can be used alone or in combination with insulin, metformin, and sulfonylureas in people with type 2 diabetes.

Dosing

Note that onset of action is delayed by several weeks, perhaps as many as 8-12 weeks.

Pioglitazone:  Start at 15-30 mg/day by mouth.  Maximum dose is 45 mg/day.

Rosiglitizone:  Start at 4 mg/day by mouth.  After 8-12 weeks, dose may be increased to 8 mg/day.

Side effects

Weight gain is fairly common, through both fluid retention and increase in fat tissue.  Weight gain with pioglitazone, for example, is around 6–12 pounds (3–5 kg).  Mild anemia and puffy feet and hands (edema from fluid retention) are also seen.  Fluid retention may ultimately cause congestive heart failure.  This drug-induced fluid retention does not respond very well to fluid pills (diuretics).

The combination of insulin injections and TZD may increase the risk of heart failure.

Some studies suggest that rosiglitazone increases the risk of heart attacks, heart failure, and death.  That’s why the Food and Drug Administration in 2011 drastically curtailed use of the drug. The FDA re-examined the date in 2013 and decided that rosiglitazone didn’t increase cardiovascular risk after all.

Preliminary data suggest a link between bladder cancer and pioglitazone.

TZDs are associated with increased risk for broken bones, perhaps doubling the risk.

Macular edema—manifested by blurry vision—may occur infrequently.

When used as the sole diabetic medication, TZDs do not cause hypglycemia.  But when used with insulin injections or insulin secretagogues, low blood sugar can occur.

Don’t use if you . . .

. . . have a significant degree of congestive heart failure or active liver disease.  Even a history of heart failure may be a reason to avoid TZDs.  TZDs should probably not be used in women with low bone density or anyone else prone to fractures.

Steve Parker, M.D.

Updated December 26, 2013

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February 4, 2010 · 2:00 AM

Red Wine With Meaty Meals Possibly Healthier Than Wine and Meat Alone

Meaty meal in the making
Meaty meal in the making

 Wine is a time-honored component of the healthy Mediterranean diet and, traditionally, is consumed with meals.

For science and food geeks, Bix at the Fanatic Cook blog has a post outlining how red wine consumption with meals might be healthy: it reduces blood levels of cytotoxic lipid peroxidation products like malondialdehyde.

By no means is Fanatic Cook always this esoteric.  Check out some of the other topics there.

Steve Parker, M.D.

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February 3, 2010 · 11:23 AM

Drug Review: Metformin

metformin for type 2 diabetesMetformin is a major drug for treatment of type 2 diabetes.  In fact, it’s usually the first choice when a drug is needed. 

This review is quite limited—consult your physician or pharmacist for full details.  Remember that drug names vary by country and manufacturer.  Glucophage is a common brand name for metformin in the U.S. 

Class

Biquanide (it’s the only one in this class).

How does it work?

In short, metformin decreases glucose output by the liver.  The liver produces glucose (sugar) either by breaking down glycogen stored there or by manufacturing glucose from smaller molecules and atoms.  The liver then kicks the glucose into the bloodstream for use by other tissues.  Insulin inhibits this function of the liver, thereby keeping blood sugar levels from getting too high.  Metformin improves the effectiveness of insulin in suppressing sugar production.  In other words, it works  primarily by decreasing the liver’s production of glucose.

Physicians talk about metformin as an “insulin sensitizer,” primarily in the liver but also to a lesser extent in peripheral tissues such as fat tissue and muscle.  It doesn’t work without insulin in the body.

Metformin typically lowers fasting blood sugar by about 20% and hemoglobin A1c by 1.5% (absolute decrease, not relative).

When used as the sole diabetic medication, metformin is associated with decreased risk of death and heart attack, compared to therapy with sulfonylureas, thiazolidinediones, alpha-glucosidase inhibitors, and meglitinides.

Not uncommonly, metformin leads to a bit of weight loss and improved cholesterol levels.  Insulin and sulfonylurea therapy, on the other hand, typically lead to weight gain of 8–10 pounds (4 kg) on average.

Usage

Metformin works by itself, but can also be used in combination with most of the other diabetic medications.  It’s usually taken 2–3 times daily.

Dose

Starting dose is typically 500 mg taken with the evening meal.  The dose can be increased every week or two.  If more than 500 mg/day is needed the second dose—500 mg—is usually given with breakfast.  Usual effective maximum dose is around 2,000 mg daily.

Side effects

Metallic taste, diarrhea, belly pain, loss of appetite.  Possible impaired absorption of vitamin B12, leading to anemia.  When used alone, it has very little risk of hypoglycemia.  Rare: lactic acidosis.

Don’t use metformin if you have . . .

Impaired kidney function (keep reading), congestive heart failure of a degree that requires drug therapy (this is debatable), active liver disease, chronic alcohol abuse.

Regarding impaired kidney function: don’t use metformin if your eGFR (estimated glomerular function rate) is under 30 ml/min/1.73 m squared), and use only with extreme caution if eGFR drops below 45 while using metformin. Don’t start metformin if eGFR is between 30 and 45. Your doctor can calculate your eGFR and should do so annually if you take metformin.

Steve Parker, M.D.

Updated April 10, 2016

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