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Journal of the American Academy of Physician Assistants:
Case Report

Switching a hyperinsulinemic patient from insulin to oral hypoglycemics

Nixon, Alexis PA‐C

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Author Information

Alexis Nixon is director of health education for Ideal Healthcare clinic, Los Angeles, california, and CEO of Uklex Inc, also in Los Angeles.

No relationships to disclose.

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Careful investigation of the nature of the patient's diabetes allowed her to move from insulin to oral therapy with metformin, improving her health and quality of life.

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A 46‐year‐old female living in an adult residential facility for the developmentally disabled (ARF‐DD) was seen at the facility for routine initial evaluation, tuberculosis (TB) screening (ie, TB skin test), and completion of forms required by both the California Department of Social Services (CDSS) and the California Department of Developmental Services (CDDS). According to facility records, the patient's medical history included moderate mental retardation, seizure disorder, dyslipidemia, gastritis, hypertension, depression, psychosis, rhinitis, and diabetes mellitus (DM). She had no known allergies. Her medications included carbamazepine, levetiracetam, lacosamide, simvastatin, omeprazole, amlodipine, perphenazine, trihexyphenidyl, fluoxetine, trifluoperazine, and human insulin (Humulin) 70/30. There was no history of tobacco, alcohol, or illicit drug use.

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Physical examination

Findings on examination were significant only for appendectomy scar, obesity, and trace bilateral pretibial edema. Vital signs were as follows: BP, 140/90 mm Hg; pulse, 76 beats per minute; respiration, 16 breaths per minute; temperature, 97.4°F. The patient was 67 in tall, weighed 240 lb, and had a body mass index (BMI) of 37.5 kg/m2.

According to the facility's staff, a home health nurse— requested by the patient's former medical provider—had been visiting the facility twice daily for the past few years to perform glucometry and administer Humulin 70/30 in a dosage of 10 units twice a day; this amount is far less than one would expect for a patient weighing 240 lb. The staff indicated that the patient was bothered by the discomfort associated with her diabetes regimen, and they suspected that the discomfort was responsible for her recurrent behavioral outbursts. There was no available documentation to indicate whether Ms. D had ever failed, or even tried, oral hypoglycemic therapy.

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Laboratory studies
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Results of studies done to assess the patient's diabetes status were significant for a fasting blood glucose, 151 mg/dL; glycosylated hemoglobin (A1C), 6.2%; C‐peptide, 7.26 ng/dL (reference range, 0.80‐3.10 ng/dL). The patient was unable to provide a urine sample. Although glucometry results recorded by the home health nurse were not available for review at this evaluation, the A1C of 6.2% equated to an average daily blood glucose level of 126 mg/ dL over the preceding 3 months and indicated good glycemic control.

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The combined findings of good glycemic control despite using such a small amount of Humulin 70/30, a body phenotype more typical of someone with type 2 diabetes mellitus, and reports of the patient's recurrent discomfort raised a question about the appropriateness of her insulin regimen. This question became compelling upon review of the C‐peptide elevation, which indicated that the patient's beta cells were not merely functioning, they were hypersecreting. The patient was therefore hyperinsulinemic—a status attributable solely to her endogenous insulin production. In the setting of her hyperglycemia, the hyperinsulinemia suggested a concomitant degree of insulin resistance.

Eight days after the evaluation, the decision was made to switch the patient from insulin to an oral hypoglycemic agent. The Humulin 70/30 was changed to Humulin R to be administered on a sliding scale (Table 1), and she was prescribed metformin 500 mg daily. The home health agency was advised to continue twice‐daily glucometry and to implement the insulin sliding scale, if indicated. In addition, a diet plan (Table 2) was provided to the facility, along with an explanation of its components. As usual, the patient would continue to be supervised at all times, whether she was at home in the ARF‐DD, attending a day program, or on an outing; this provided an added layer of reassurance during the transition period.

Table 1
Table 1
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Table 2
Table 2
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Five days after the change in treatment was instituted, the patient's capillary glucose peaked at 154 mg/ dL (calculated daily average, 139 mg/dL), at which point her metformin was increased to 500 mg twice daily. Over the 9 days following the metformin increase, the calculated daily capillary glucose average was down to 117 mg/dL, and on the ninth day, her fasting C‐peptide had also decreased to 7.09 ng/dL. These results suggested that the patient's glycemic control had improved even though she was secreting less insulin; the efficacy of her endogenous insulin had thus improved. As of the writing of this article, use of the Humulin R has not been necessary.

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- Compared with oral hypoglycemic agents, insulin treatment is generally associated with increased cost, pain, inconvenience, psychological burden, and potential for complications. Therefore, whenever possible and when not contraindicated, oral hypoglycemics are preferable to insulin in facility residents who have diabetes mellitus.

- In a patient who is using only insulin to treat dm, an elevated serum c‐peptide level might suggest that beta cells are still secreting insulin and therefore cast doubt on the appropriateness of insulin therapy.

- Whereas defects in beta‐cell secretion generally result in hypoinsulinemia and hyperglycemia, insulin resistance often results in hyperinsulinemia and comparatively less predictable glucose levels (hyperglycemia, euglycemia, or even hypoglycemia).

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In California, many dependent adults—particularly those who have a mental or developmental disability—live in statelicensed residential care facilities. Examples include but are not limited to adult residential facilities for the mentally ill (ARF‐MIs), adult residential facilities for the developmentally disabled (ARF‐DDs), and residential care facilities for the elderly (RCFEs). In accordance with staffing guidelines outlined in Title 22 of the California Code of Regulations (CCR), a majority of California ARFs and RCFEs are staffed by unlicensed personnel. Among numerous other restrictions on medical care, Title 22 CCR (section 80092.8) stipulates that unlicensed personnel are prohibited from directly drawing insulin into a syringe and administering insulin to residents; instead, unlicensed personnel are permitted only to directly perform glucometry using a glucometer approved by the FDA. Unlicensed personnel are also permitted to provide assistance (ie, set up the insulin, clean up after the patient has self‐administered, and record values) to residents who are able to perform insulin draw‐up and administration themselves.1 For residents who are cognitively or physically unable to self‐perform such procedures, home health nursing services must be contracted. If insurance or funding does not permit these costly services, the resident may have to be moved to a higher, more restrictive level of care, which would involve a less homelike living environment. Compared with oral hypoglycemic agents, insulin treatment is generally associated with increased cost, pain, inconvenience, psychological burden, and potential for complications. Accordingly, Hohberg and colleagues describe insulin as “the last treatment option, when oral treatment fails to provide stable [glycemic] control.”2 Therefore, whenever possible and when not contraindicated, oral hypoglycemics are preferable to insulin in facility residents who have diabetes mellitus.

Proinsulin is produced in and secreted from the pancreas, specifically the beta cells of the islets of Langerhans.3 From proinsulin, equimolar amounts of insulin and connecting peptide (C‐peptide) are cleaved.4 Because of significant hepatic uptake, direct measurement of insulin from the peripheral circulation does not accurately reflect the amount of insulin present in the portal circulation. In comparison, lacking the same significant hepatic uptake, C‐peptide levels in the peripheral circulation more accurately approximate portal circulatory levels of C‐peptide. Given the equimolar production of insulin and C‐peptide, quantitative measurement of C‐peptide in the peripheral blood can be used as a surrogate for the quantitative measurement of beta‐cell function,4 that is, insulin secretion, particularly when combined with concurrent glucose measurement and dietary‐intake data. Exogenous insulin preparations, such as Humulin 70/30, do not contain C‐peptide and thus do not contribute to an elevated serum C‐peptide level. Therefore, in a patient who is using only insulin to treat DM, one would not expect to find an elevated serum C‐peptide level; such a finding would suggest—among other possibilities—that the patient's beta cells are still secreting insulin and therefore cast doubt on the appropriateness of insulin therapy.

According to the American Diabetes Association (ADA), there are two major types of diabetes mellitus (type 1 [T1DM] and type 2 [T2DM]) and several subtypes (gestational diabetes, latent autoimmune diabetes of adults [LADA], and chemical‐ or drug‐induced diabetes).5 A diagnosis of T1DM implies that the patient is not secreting enough endogenous insulin and is thus dependent on exogenous insulin. Although T1DM can occur at any age, it typically begins during childhood and results from autoimmune destruction of the beta cells.

In contrast, the pathogenesis of T2DM is multifactorial. A diagnosis of T2DM infers that endogenous insulin is still being secreted, but there are defects in the secretory process and/or insulin function. Whereas beta‐cell secretory defects generally result in hypoinsulinemia and hyperglycemia, insulin dysfunction (ie, insulin resistance) often results in hyperinsulinemia and comparatively less predictable glucose levels (hyperglycemia, euglycemia, or even hypoglycemia).

In a patient with insulin resistance, the pancreas initially tries to compensate by producing more insulin—and therefore more C‐peptide—thus leading to hyperinsulinemia. Although this compensatory measure is intended to be physiologic— ie, to reduce hyperglycemia and increase cellular uptake of glucose—it has pathophysiologic consequences. In their paper, Hohberg and colleagues point out an “independent association between insulin resistance [hyperinsulinemia] and subclinical or clinical coronary heart disease.”2 Likewise, researchers led by Okamoto report that hyperinsulinemia is “an independent risk factor for macrovascular disease … [as well as] accelerated cognitive decline and dementia.”6 The morbidity associated with hyperinsulinemia could lead to a presumption that administering additional insulin in the setting of hyperinsulinemia might further compound morbidity; although this conclusion is not illogical, a presumption of such magnitude would need to be further validated before gaining widespread acceptance.

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Given the insulin resistance indicated by this patient's hyperinsulinemia and hyperglycemia, a favorable response to metformin was expected. What she needed was not more insulin; she was already producing greater than normal amounts. Instead she needed treatment that would enable her endogenous insulin to function more effectively, that is, to overcome the resistance. In accordance with published guidelines, metformin was prescribed as the firstline oral hypoglycemic; it is purported to decrease glucose absorption and gluconeogenesis and—more specific to our patient's needs—to increase hepatocellular insulin sensitivity.5 Although the response to metformin monotherapy and the diet plan was expected to be favorable, it was not predicted to be entirely sufficient. From the outset, the thought was that the patient's C‐peptide and possibly her glucose level would increase dramatically, thus necessitating an add‐on insulin sensitizer, such as pioglitazone. This was not the case, however. The patient's T2DM remains stable on metformin 500 mg twice daily.

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Take‐home message

PAs who are treating DM—or any other pathologic condition—must comprehend the underlying pathophysiologic mechanism(s) and target therapy accordingly because how one gets to goal is arguably as important as arriving at goal. Furthermore, when constructing or implementing a therapeutic plan, careful consideration should also be given to factors external to the disease process, especially quality of life.

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1. California Department of Social Services. Residential regulations. Accessed November 7, 2012.

2. Hohberg C, Pfützner A, Forst T, et al. Successful switch from insulin therapy to treatment with pioglitazone in type 2 diabetes patients with residual beta-cell function: results from the PioSwitch Study. Diabetes Obes Metab. 2009;11(5):464-471.

3. Ganong WF. Review of Medical Physiology. 21st ed. New York, NY: McGraw-Hill; 2003.

4. American Association for Clinical Chemistry. C-peptide. Lab Tests Online Web site. Last reviewed April 14, 2010. Last updated April 28, 2011. Accessed November 7, 2012.

5. American Diabetes Association. Standards of medical care in diabetes-2011. Diabetes Care. 2011;34 Suppl 1:S11-S61.

6. Okamoto T, Okamoto L, Lisanti MP, Akishita M. Switch to oral hypoglycemic agent therapy from insulin injection in patients with type 2 diabetes. Geriatr Gerontol Int. 2008;8(4):218-226.

© 2012 Lippincott Williams & Wilkins, Inc.


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