Insulin resistance to diabetes: Does it have to occur? What are the initial treatment steps?

W. Lane Edwards, Jr, MSN, ARNP, ANP
Hospitalist, The Hospitalist Group of Southwest Florida, LLC
Fort Myers, Florida

Case

Jill is a 35-year-old single mother who presents to our clinic. Her lab workup reveals the following:

• Fasting blood glucose (FBG): 103 mg/dL; average of 146 mg/dL 2 hours post-meal
• Waist circumference: 42 inches
• Blood pressure (BP): 140/84 mm Hg, on 2 occasions
• Low-density lipoprotein cholesterol (LDL-C): 130 mg/dL
• High-density lipoprotein cholesterol (HDL-C): 39 mg/dL
• Triglycerides: 210 mg/dL
• Alanine aminotransferase (ALT): 75 mg/dL
• Aspartate aminotransferase (AST): 50 mg/dL.

Discussion

The primary defects associated with abnormal glucose disposal are inappropriate amounts of glycogen secreted from the liver and insulin resistance. The medical literature suggests that insulin resistance—the inability of insulin to adequately transport glucose from the vascular system to the tissues—leads to a state in which a given increase in plasma insulin levels results in less of an effect in blood glucose lowering. Insulin resistance is the primary cause of glucose disposal issues in individuals like Jill.¹

Central adiposity (waist circumference >35 inches in a female) and poor physical conditioning account for 50% of insulin-resistant individuals.² Genetic factors can also play a role. Is Jill insulin resistant? There are several ways to assess her insulin resistance with the data provided thus far. One method is to divide the triglycerides level by the HDL level—if the result is >3.5, the patient is insulin resistant.³ Jill’s result is 5.38. The presence of abnormal liver functions (ALT greater over normal than the AST with the absence of sonographic abnormalities and with a normal hepatitis panel) would suggest fatty liver or nonalcoholic steatohepatitis (NASH). The primary cause of NASH is insulin resistance.⁴ Insulin resistance is the cause of Jill’s glucose disposal issues.

The literature also suggests that early and aggressive intervention in glucose disposal issues decreases target organ damage in the future.⁵ The first intervention is to help the patient understand the concept of glucose disposal, insulin resistance, and nonpharmacologic interventions to reduce insulin resistance as much as possible. We’ve counseled Jill on the importance of (1) dietary education (ie, appropriate intake of carbohydrates, fat, and protein); (2) the correlation of diet to blood sugars (ie, occasional fasting, but primarily post-meal)⁵; and (3) the initiation of a physical conditioning program based on her baseline physical activities. Walking 2 miles in about 30 minutes 6 to 7 days per week will decrease central adiposity.

Case

At her follow-up visit 2 months later, Jill states that she has given us her “best and consistent” effort with her diet and exercise plan. Her lab work is as follows:

• FBG: 118 mg/dL; average of 140 to 150 mg/dL post-meal
• Waist circumference: 40 inches
• HDL: 41 mg/dL
• Triglycerides: 180 mg/dL.

Oral pharmacologic intervention is designed to stimulate beta-cell production of insulin (sulfonylureas, meglitinides, dipeptidyl peptidase-4 [DPP-4] inhibitors), decrease insulin resistance (thiazolidinediones [TZDs] or biguanides), decrease hepatic overproduction of glucose (TZDs, biguanides, or DPP-4 inhibitors), or decrease glucose absorption in the gut (α-glucosidase inhibitors or biguanides).⁶ Where should you start?

Based on Jill’s primary defect, simply increasing insulin production may result in hypoglycemia and could decrease beta-cell effectiveness in the future. The side effects of α-glucosidase inhibitors (eg, significant flatulence) generally decrease compliance. The most effective initial oral pharmacologic agents for Jill is a combination of a biguanide and a TZD. This regimen will decease inappropriate glucose input from her liver, thereby decreasing insulin resistance. These agents are available commercially as a combination pill with varying doses.

Jill should be taught that, in combination with her diet and physical conditioning, these agents would be expected to influence her blood sugars within 12 weeks of initiation. The advanced practice clinician should make Jill aware that pregnancy is not recommended while taking these agents. These agents may also cause weight gain, peripheral edema, diarrhea, and abdominal discomfort; also, the biguanide component must be discontinued for before undergoing any procedure that uses contrast media.

Jill’s follow-up in 12 weeks was remarkable:

• FBG: 89 mg/dL; average 127 mg/dL post-meal
• Waist circumference: 38 inches
• BP: 120/72 mm Hg
• LDL: 103 mg/dL
• HDL: 46 mg/dL
• Triglycerides:140 mg/dL.

Summary

If Jill continues on this path, it is foreseeable that, if insulin resistance was a key factor in her glucose disposal issues, that her disease process will not escalate to diabetes. Minimal additional therapy may be needed in the future to maintain euglycemia and decrease target organ damage from her glucose disposal issues.

R E F E R E N C E S

1. National Diabetes Information Clearinghouse (NDIC). Insulin resistance and pre-diabetes. October 2008. NIH publication 09-4893. http://diabetes.niddk.nih.gov/DM/pubs/insulinresistance/. Accessed August 12, 2009.
2. Bloomgarden ZT. The 1st World Congress on the Insulin Resistant Syndrome. Diabetes Care. 2004;27:602-609.
3. McLaughlin T, Reaven G, Abbasi F, et al. Is there a simple way to identify insulin-resistant individuals at increased risk of cardiovascular disease? Am J Cardiol. 2005;96:399-404.
4. National Digestive Diseases Information Clearinghouse (NDDIC). Nonalcoholic steatohepatitis. November 2006. NIH publication 07-4921. http://digestive.niddk.nih.gov/ddiseases/pubs/nash/. Accessed August 12, 2009.
5. University of Southern California. Early intervention stops damage to insulin-producing cells in women at high risk for type 2 diabetes. Science Daily. June 17, 2002. http://www.sciencedaily.com/releases/2002/06/020617075530.htm. Accessed August 5, 2009.
6. American Diabetes Association. Other diabetes medications. http://www.diabetes.org/type-2-diabetes/oral-medications.jsp. Accessed August 5, 2009.