Tag Archives: glargine

September 15, 2011 · 2:00 AM

The Holy Grail of Diabetes Treatment: Preserving Beta Cell Function

 A Nobel Prize in Medicine belongs to whoever (whomever?) figures out how to reliably and affordably protect and preserve beta cell function starting early in the course of type 2 diabetes.  Or type 1 diabetes, for that matter.

Dietary carbohydrates lead to secretion of insulin into the bloodstream by the pancreas’s beta cells.  The insulin limits and reverses the rise in blood sugar that results from digestion of carbohydrates.  If blood sugar rises too high, it damages our bodies. 

Type 2 diabetes is a disorder of carbohydrate metabolism.  Insulin from the beta cells isn’t doing its job adequately because tissues that should be taking up bloodstream sugar are resistant to insulin’s effect of driving sugar into the cells.  The beta cells pump out increasing amounts of insulin, trying to overcome the resistance of the tissues.  Eventually the beta cells become exhausted or “burned out,” reflected in diminished beta cell mass.  This situation has usually been present for years before type 2 diabetes is formally diagnosed.  This scenario is a leading theory of the development of type 2 diabetes.

Type 2 diabetes is considered by most physicians to be a progressive illness, requiring more and more drugs to control as the years pass.  That’s because the beta cells are dying off or otherwise becoming totally nonfunctional.  Once they’re gone, it’s hard (impossible?) to get them back.  If diabetes could be diagnosed early on, we’d find healthier beta cells to work with.  Perhaps we could strengthen or protect them.  This is what beta cell preservation is all about.  Keep them working as nature intended, avoiding the expense and risks of drug therapy.

So I was excited to find an article entitled “Effects of exenatide on measures of beta cell function after three years in metformin-treated patients with type 2 diabetes.”  Exenatide is sold in the U.S. as Byetta.  It’s a GLP-1 analogue.  

European researchers studied 36 type 2 diabetics for three years.  All were taking metformin.  Sixteen of them also took exenatide, whereas 20 also took insulin glargine (e.g., Lantus in the U.S.). 

What Did They Find?

Both groups achieved similar levels of blood sugar control after three years.  Exanatide users lost 5.7  kg (12.5 lb) while glargine users gained 2.1 kg (4.6 lb). 

After three years of drug use, the subjects were told to stop exenatide and glargine while continuing metformin. After four weeks off-drug:

  • insulin sensitivity improved significantly in the exenatide group while glargine had no effect
  • first-phase insulin secretion improved by a small amount in the exenatide group

However, 12 weeks after stopping the study drugs, hemoglobin A1c and fasting blood sugars returned to pretreatment levels in both groups.  (Hemoglobin A1c is a blood test of overall diabetes control over the preceeding three months.)   

Final Thoughts

You have to wonder if the improved insulin sensitivity in the exenatide group simply reflects their weight loss as compared to the weight gain in the insulin glargine group.  Improved insulin sensitivity is good, any way you can get it. 

ResearchBlogging.orgWhen measured 12 weeks after stopping the study drugs, hemoglobin A1c and fasting blood sugar levels were no better than baseline levels three years earlier.  Very disappointing.  If exanatide or glargine preserved beta cell function, you’d want to see better post-treatment numbers.  The search for beta cell preservation continues.

Steve Parker, M.D.

Reference: Bunck, M., Corner, A., Eliasson, B., Heine, R., Shaginian, R., Taskinen, M., Smith, U., Yki-Jarvinen, H., & Diamant, M. (2011). Effects of Exenatide on Measures of Beta-Cell Function After 3 Years in Metformin-Treated Patients With Type 2 Diabetes Diabetes Care, 34 (9), 2041-2047 DOI: 10.2337/dc11-0291

PS: In case it matters to you, this study was funded at least partially by Amylin Pharmaceuticals and Eli Lilly and Company.

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September 15, 2010 · 2:00 AM

Drug Review: Insulin

Insulin is life-saving for type 1 diabetics.  Many type 2 diabetics will eventually, if not at the outset, need to take insulin for adequate control of blood sugars, which should help prevent diabetes complications.

My comments here are simply a brief review of insulins used by type 2 diabetics.  Anyone taking insulin must work closely with a physician or diabetes nurse educator on proper dosing, injection technique, and recognition and management of hypoglycemia (low blood sugar).

This is NOT an insulin rig! Modern insulin injections barely hurt, if at all.

Insulin’s Mechanism of Action
 

 

 

Insulin is made by the pancreas to keep blood sugars from rising above a fairly strict range: 70-140 mg/dl or 3.89-7.78 mmol/l.  [It has many other actions that I won’t bother to outline here.]  When we eat a meal containing carbohydrates (and proteins to a lesser extent), blood sugar starts to rise as we digest the carbs.  Insulin drives the sugar into our body’s cells for use as immediate energy or conversion to fat as stored energy.  About half of the insulin produced by a healthy body is “basal,” meaning it’s secreted into the bloodstream in a steady, low-volume amount, to keep the liver from making too much sugar (glucose) and controlling fasting sugar levels.  The other half is secreted in to the bloodstream in response to meals.

In type 2 diabetes, the body’s tissues, at first, are resistant to the effect of insulin.  So the pancreas has to secrete more than usual (hyperinsulinism). As the illness progresses, the pancreas cannot keep up with demand for more insulin and starts to “burn out,” producing less insulin.  This is when many type 2 diabetics need to start insulin injections.  [These are generalities; there are exceptions.]

Types of Insulin

Specific names of insulins vary by manufacturer and by country.  By convention, I capitalize only the brand names below, plus NPH and NPL.

We could break them down into two types: human (identical in structure to human insulin) and analogs (minor molecular modifications to the usual human insulin molecule).  But most people don’t care about that.  It’s more helpful to distinguish them by the timing of their action:

  • Rapid acting:  lispro (e.g., Humalog), aspart (e.g., Novolog), glulisine (e.g., Apidra)
  • Short acting:  regular (e.g., Novolin R, Humulin R)
  • Intermediate to long acting:  NPH, glargine (e.g., Lantus), detemir (e.g., Levemir), degludec (e.g., Tresiba), NPL (neutral protamine lispro)

Rapid-acting insulins have onset of action between 5 and 15 minutes, peak effect in 30 to 90 minutes, and duration of action of 2 to 4 hours.

Short-acting “regular insulin” has  onset in 30 minutes, peaks in 2 to 4 hours, and works for 5 to 8 hours.

Intermediate to long-acting insulins start working in 2 hours, don’t have a well-defined peak of action, and may keep working for 20 or more hours (glargine), for 6 to 24 hours (detemir), or 30 to 42 hours (degludec).

All these times are gross approximations.  Once the insulin is injected into the fat below the skin, it has to be absorbed into the bloodstream and transported to the tissues where it does its magic.  Lots of factors affect this process. For instance, the thicker the fat tissue at the injection site, the slower the absorption.  Absorption tends to be  faster from the abdominal wall, slower from the arms, even slower from the thighs or buttocks.  Absorption can vary from day to day in an individual even when injection site and technique are identical.

As you might have guessed, the short- and rapid-acting insulins are usually injected before a meal in anticipation of blood sugar rising as food is digested.  The intermediate- and long-acting insulins imitate the healthy body’s “basal” insulin.

Manufacturers also supply premixed insulins, combining intermdiate or long-acting insulin with a short- or rapid-acting insulin.  Examples are Humalog 75/25, Humulin 70/30, and Novolog 70/30.

Dose and Selection of Insulin

See your physician or diabetes nurse educator for details.  Many type 2 diabetics get started just with an intermediate or long-acting insulin once or twice daily, with or without diabetes drugs by mouth. Nearly all type 1’s will need a long-acting “basal” insulin (one-third to one-half of their total daily insulin requirement, plus meal-time “bolus” dosing with a rapid-acting insulin. Insulin pumps are a topic for another day.

Side Effects

By far the most common and worrisome is hypoglycemia.

Steve Parker, M.D.

Last update: August 1, 2016

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