Timothy S. Reid, MD

Type 2 diabetes mellitus (T2DM) is a chronic, progressive disease that is primarily characterized by peripheral insulin resistance, hepatic gluconeogenesis, and progressive Î²-cell failure. There are numerous other organ systems involved in glucose regulation including the gut, kidneys, and brain. For many patients with T2DM, use of oral medication early in their disease process will modify or improve one or more of these defects. With time, however, as Î²-cell function declines, insulin production wanes, making it increasingly likely that hormone replacement in the form of insulin administration will be necessary. With this in mind, here are 5 scenarios that indicate your patient may benefit from the initiation of insulin therapy. 

1. Your patient has been taking 2 oral agents for 6 months and A1C levels are routinely elevated

There are 2 options at this stage of treatment.  You can add a third oral agent-and that can be one chosen from a class of antihyperglycemic medications that hasn’t yet been tried. But a typical problem enters here: The majority of patients we see in primary care have typically had T2DM for some time. A central defect in T2DM, loss of Î²-cell function, will be advanced at this stage and hence insulin production will be decreasing. The potential for T2DM-related complications is also increasing with sustained hyperglycemia. It’s likely the patient will be getting frustrated about not reaching established diabetes goals-and the clinician may be, too.  In my experience, if the A1C exceeds 8.5%, adding a third oral agent will not get your patient to goal. 

 for treatment of hyperglycemia from the ADA/EASD recommend advancing therapy after 3 months if the patient is not at goal. This is an excellent time to continue your discussion about insulin therapy with your patient. Insulin stands out among antihyperglycemic agents in its ability to lower A1C values up to 3.5%. I strongly encourage you and your patient to consider the addition of a basal insulin if your A1C goals are not met with 2 oral agents after 3 months of therapy.

2. Your patient has had T2DM diabetes for 6 years or longer

Progressive Î²-cell function decline is the natural course of T2DM and is said to begin as many as 12 years before a diagnosis is made. The critical point here is that this progression continues 

United Kingdom Prospective Diabetes Study

 both showed a decrease in Î²-cell function during the first 5 to 10 years after the diagnosis of T2DM and a consequent deterioration in glycemic control. UKPDS participants were taking metformin, SFUs, or insulin and had initially good responses that declined over time. Many of your patients will be in this portion of their “diabetes life-cycle.” The 

) demonstrated a deterioration in glycemic control over time with monotherapy using metformin, rosiglitazone, and glyburide. More than likely, many of your patients will have been on one or more of these medications since diagnosis. Estimates are that A1C will 

approximately every 2 years with most therapies. It is so important to use effective medications at each stage of the disease.  Think about patients you’ve been treating for a while and how well controlled they are. Is it time to talk about insulin? Most patients will respond positively to the addition of insulin at this stage. 

3. Your tall, thin patient is not responding to oral antidiabetic medications

It is important to consider the basics when you are evaluating a patient diagnosed with diabetes who is unresponsive to oral medication. Many patients are diagnosed with adult-onset diabetes after testing positive for elevated blood sugar. Oral diabetes medication is started and there is little more thought given to the situation. Unfortunately, a significant number of people are misdiagnosed as having T2DM when the actual underlying disease is latent autoimmune diabetes of the adult (LADA). In 

 48% of young (mean age, 33 years), non-obese patients with diabetes, a negative family history, and a progressive deterioration in glycemic control actually had LADA. LADA is a variant of type 1 diabetes in which the body’s immune response attacks Î²-cells causing insulin deficiency. The loss of blood sugar control happens more slowly in young adults than in children and is likely the reason it is frequently missed.  There are signs that should trigger clinical suspicion: Patients with LADA typically do not demonstrate the characteristics of metabolic syndrome (obesity, hypertension, hyperlipidemia). They respond poorly to medications that are predicated on a functioning Î²-cell and so A1C will continue to climb. These patients are treated best when they are correctly diagnosed in a timely manner. If you think there is something other than T2DM at work, check for anti-GAD 65 antibodies, islet cell antibodies, and IA-2a antibodies. A positive result to any of these is evidence of an immune attack on pancreatic Î²-cells. The correct medication approach is immediate initiation of insulin. Oral ant-diabetic medications can be discontinued. These patients should be introduced to the diabetes care team for comprehensive management.

Prolonged high blood sugar and uncontrolled A1C may manifest as persistent fatigue. It is not uncommon for one of my new patients to complain of significant fatigue that has been present for anywhere from a few months to a number of years. Even patients who are suboptimally controlled on insulin therapy can demonstrate excess fatigue. Switching to insulin therapy and titrating for glycemic control, can, in many cases, mitigate the constant weariness. As a side note, it is important to make this connection for the patient between insulin deficiency and fatigue. If the patient sees rapid symptom improvement the motivation for adherence to insulin therapy may be much greater.

5. Your patient’s comorbid conditions are narrowing your choice of oral medication to treat T2DM

Patients almost never present with isolated T2DM. More than likely they will have other serious health issues including cardiovascular, renal, and gastrointestinal problems that evolve over time as diabetes progresses. All oral diabetes medications have side effects and contraindications to consider in light of the many typical comorbid conditions. I have seen patients suffer with gastrointestinal distress for years and no one questioned the metformin. Patients develop renal insufficiency as they age and have had diabetes for some time and the medications are not adjusted. Medications should be reviewed regularly and particularly in the context of changes in health. In fact, the sicker the patient, the more likely insulin is to be an appropriate medication for them.

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Progressive  β-cell failure is a core defect of type 2 diabetes; most patients will eventually need insulin replacement therapy. When is the right time? Here, 5 scenarios that may help you make a decision. 

Timothy S. Reid, MD

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