Emergency Management of New-Onset Type 2 Diabetes
Emergency Management of New-Onset Type 2 Diabetes
I am associate professor of emergency medicine in a community teaching hospital and I frequently have a difficult time convincing internal medicine residents to admit middle-aged obese patients with new-onset severe hyperglycemia (> 500 but < 700 mg/dL) without metabolic acidosis or other comorbidities.
These patients primarily present with polyuria and polydypsia and no other symptoms. The glucose levels are easily lowered by administering fluid and a one-time subcutaneous dose of regular insulin. The internal medicine consult usually recommends starting the patient on glyburide, a treatment with variable reliability on close follow-up.
In adult-onset type 2 diabetes, should insulin be started only after oral agents fail?
What would be the expected failure rate with oral hypoglycemic agents in patients with adult-onset type 2 diabetes with high random serum glucose levels, and is the magnitude of the glucose elevation prognostic of oral agent failure?
What is the difference in success of diabetic teaching programs in an outpatient setting (loosely controlled outpatient model) vs an inpatient model?
Mark Clark, MD
There are several issues unique to patients newly diagnosed with type 2 diabetes who present to emergency and urgent-care physicians. The first treatment question is whether insulin should be started only after oral agents fail. When a patient presents with severe hyperglycemia, glucose toxicity may be a major issue affecting the course of treatment. Often these patients have been hyperglycemic for weeks or months prior to presenting with the usual symptoms of polyuria and polydipsia. During this time, the pancreatic beta cells are desensitized to glucose-stimulated insulin secretion due to the persistently high ambient glucose concentrations, resulting in insufficient insulin production and availability.
However, glucose toxicity is at least partially reversible, and this has major implications in the choice of an initial treatment. Many patients with severe glucose toxicity are best managed by insulin therapy because of their relative lack of endogenous insulin secretion and underlying insulin resistance that is exacerbated by glucose toxicity. As the effects of glucose toxicity are reduced over the first few weeks of treatment, the insulin dose can be tapered and oral medications may be successfully introduced. If a patient presents with less severe hyperglycemia, a sulfonylurea, given either at high or maximal dose, may increase endogenous insulin secretion, enough to control glucose levels.
When considering other commonly used classes of oral medications for patients who present with severe hyperglycemia, their mechanisms of action must be taken into account. The thiazolidinediones, rosiglitazone and pioglitazone, function in part by improving insulin resistance through activation of peroxisome proliferator-activated receptor (PPAR)-gamma, which is a nuclear receptor that affects gene expression and promotes glucose uptake in skeletal muscle tissue. However, because it may take up to 4-6 weeks to achieve the full therapeutic effect, these agents may not be helpful for initial management in patients with severe hyperglycemia. Metformin decreases hepatic glucose output and does not promote weight gain. However, metformin may not be ideal in patients initially presenting with severe hyperglycemia and glucose toxicity because it does not stimulate insulin secretion and it can take 1-3 weeks to see the full therapeutic effect.
Therefore, subcutaneous insulin or high-dose sulfonylureas are often the initial therapies of choice in patients with severely elevated glucose levels, at least until the effects of glucose toxicity improve. Once glucose levels improve, the goal is to taper the insulin or high-dose sulfonylurea regimen and try to maintain glycemic control with either metformin and/or a thiazolidinedione. If this is not possible, then these drugs will need to be used in combination with either a sulfonylurea or, if there is insufficient beta-cell reserve, with insulin. It should be noted that pioglitazone is the only thiazolidinedione that is approved for use in combination with insulin, and that thiazolidinediones should not be used in patients with liver disease or congestive heart failure.
The second question raised relates to whether the magnitude of a severe random glucose elevation is prognostic of oral agent failure. Unfortunately, severe hyperglycemia does not provide an accurate estimate of the 2 major underlying factors in type 2 diabetes, which are insulin resistance and beta-cell reserve. In a nondiabetic person, insulin stimulates glucose uptake in skeletal muscle. In type 2 diabetes, skeletal muscle is resistant to the effects of insulin. Therefore, over time, pancreatic beta cells secrete greater and greater amounts of insulin to overcome insulin resistance. Eventually beta-cell exhaustion occurs and hyperglycemia develops.
The amount of insulin resistance and beta-cell reserve is highly variable from patient to patient at presentation. Once glucose toxicity is reduced, patients often have enough residual beta-cell function for oral agents to be effective. Measuring C-peptide levels can help determine the level of beta-cell reserve, as C-peptide is only produced if insulin is secreted by the beta cell. However, this is not always a reliable test because glucose toxicity may suppress C-peptide levels. In addition, tests can be done to determine if the patient develops late-onset type 1 diabetes due to an underlying autoimmune destruction of beta cells. Oral agents are not effective in these patients. The most helpful test when autoimmune disease is suspected involves measuring glutamic acid decarboxylase (GAD) antibodies because titers stay high after the diagnosis is made. Other, less specific tests measure islet cell antibodies and anti-insulin antibodies. Unfortunately, most of these samples are sent to reference labs and the results are not immediately available. Thus, severe hyperglycemia on initial presentation can be misleading because it does not provide an accurate assessment of the underlying insulin resistance and beta-cell reserve. Therefore, it should only be used as a rough estimate of the severity of the patient's diabetes at a point in time.
The final issue relates to the efficacy of diabetic teaching interventions in the outpatient vs inpatient setting. There is no doubt that diabetes self-management education is a cornerstone in the treatment of type 2 diabetes. The teaching process requires a multidisciplinary team that includes physicians, diabetes educators, dieticians, and others such as podiatrists and ophthalmologists. The goals should be to educate the patient regarding the diabetes disease process, nutritional management, physical activity, medications, glucose monitoring, and preventing and detecting complications. The success of diabetic teaching programs seems to be similar in the inpatient and ambulatory settings. A study by Muller and colleagues examined this question in a total of 140 patients with type 2 diabetes who received identical education programs in the 2 different settings. Patients were matched (70 ambulatory, 70 inpatient). There was no difference between the groups in regard to the improvements in HbA1c, body mass index, hypoglycemic episodes, and subsequent hospitalizations after 1 year. This suggests that education is equally effective in either setting. Furthermore, if the patient is hospitalized with other severe illnesses when diabetes is diagnosed, it may be prudent to delay diabetes education until the patient is stable and has left the hospital. Then he or she can focus full attention on the vitally important diabetes self-management education.
I am associate professor of emergency medicine in a community teaching hospital and I frequently have a difficult time convincing internal medicine residents to admit middle-aged obese patients with new-onset severe hyperglycemia (> 500 but < 700 mg/dL) without metabolic acidosis or other comorbidities.
These patients primarily present with polyuria and polydypsia and no other symptoms. The glucose levels are easily lowered by administering fluid and a one-time subcutaneous dose of regular insulin. The internal medicine consult usually recommends starting the patient on glyburide, a treatment with variable reliability on close follow-up.
In adult-onset type 2 diabetes, should insulin be started only after oral agents fail?
What would be the expected failure rate with oral hypoglycemic agents in patients with adult-onset type 2 diabetes with high random serum glucose levels, and is the magnitude of the glucose elevation prognostic of oral agent failure?
What is the difference in success of diabetic teaching programs in an outpatient setting (loosely controlled outpatient model) vs an inpatient model?
Mark Clark, MD
There are several issues unique to patients newly diagnosed with type 2 diabetes who present to emergency and urgent-care physicians. The first treatment question is whether insulin should be started only after oral agents fail. When a patient presents with severe hyperglycemia, glucose toxicity may be a major issue affecting the course of treatment. Often these patients have been hyperglycemic for weeks or months prior to presenting with the usual symptoms of polyuria and polydipsia. During this time, the pancreatic beta cells are desensitized to glucose-stimulated insulin secretion due to the persistently high ambient glucose concentrations, resulting in insufficient insulin production and availability.
However, glucose toxicity is at least partially reversible, and this has major implications in the choice of an initial treatment. Many patients with severe glucose toxicity are best managed by insulin therapy because of their relative lack of endogenous insulin secretion and underlying insulin resistance that is exacerbated by glucose toxicity. As the effects of glucose toxicity are reduced over the first few weeks of treatment, the insulin dose can be tapered and oral medications may be successfully introduced. If a patient presents with less severe hyperglycemia, a sulfonylurea, given either at high or maximal dose, may increase endogenous insulin secretion, enough to control glucose levels.
When considering other commonly used classes of oral medications for patients who present with severe hyperglycemia, their mechanisms of action must be taken into account. The thiazolidinediones, rosiglitazone and pioglitazone, function in part by improving insulin resistance through activation of peroxisome proliferator-activated receptor (PPAR)-gamma, which is a nuclear receptor that affects gene expression and promotes glucose uptake in skeletal muscle tissue. However, because it may take up to 4-6 weeks to achieve the full therapeutic effect, these agents may not be helpful for initial management in patients with severe hyperglycemia. Metformin decreases hepatic glucose output and does not promote weight gain. However, metformin may not be ideal in patients initially presenting with severe hyperglycemia and glucose toxicity because it does not stimulate insulin secretion and it can take 1-3 weeks to see the full therapeutic effect.
Therefore, subcutaneous insulin or high-dose sulfonylureas are often the initial therapies of choice in patients with severely elevated glucose levels, at least until the effects of glucose toxicity improve. Once glucose levels improve, the goal is to taper the insulin or high-dose sulfonylurea regimen and try to maintain glycemic control with either metformin and/or a thiazolidinedione. If this is not possible, then these drugs will need to be used in combination with either a sulfonylurea or, if there is insufficient beta-cell reserve, with insulin. It should be noted that pioglitazone is the only thiazolidinedione that is approved for use in combination with insulin, and that thiazolidinediones should not be used in patients with liver disease or congestive heart failure.
The second question raised relates to whether the magnitude of a severe random glucose elevation is prognostic of oral agent failure. Unfortunately, severe hyperglycemia does not provide an accurate estimate of the 2 major underlying factors in type 2 diabetes, which are insulin resistance and beta-cell reserve. In a nondiabetic person, insulin stimulates glucose uptake in skeletal muscle. In type 2 diabetes, skeletal muscle is resistant to the effects of insulin. Therefore, over time, pancreatic beta cells secrete greater and greater amounts of insulin to overcome insulin resistance. Eventually beta-cell exhaustion occurs and hyperglycemia develops.
The amount of insulin resistance and beta-cell reserve is highly variable from patient to patient at presentation. Once glucose toxicity is reduced, patients often have enough residual beta-cell function for oral agents to be effective. Measuring C-peptide levels can help determine the level of beta-cell reserve, as C-peptide is only produced if insulin is secreted by the beta cell. However, this is not always a reliable test because glucose toxicity may suppress C-peptide levels. In addition, tests can be done to determine if the patient develops late-onset type 1 diabetes due to an underlying autoimmune destruction of beta cells. Oral agents are not effective in these patients. The most helpful test when autoimmune disease is suspected involves measuring glutamic acid decarboxylase (GAD) antibodies because titers stay high after the diagnosis is made. Other, less specific tests measure islet cell antibodies and anti-insulin antibodies. Unfortunately, most of these samples are sent to reference labs and the results are not immediately available. Thus, severe hyperglycemia on initial presentation can be misleading because it does not provide an accurate assessment of the underlying insulin resistance and beta-cell reserve. Therefore, it should only be used as a rough estimate of the severity of the patient's diabetes at a point in time.
The final issue relates to the efficacy of diabetic teaching interventions in the outpatient vs inpatient setting. There is no doubt that diabetes self-management education is a cornerstone in the treatment of type 2 diabetes. The teaching process requires a multidisciplinary team that includes physicians, diabetes educators, dieticians, and others such as podiatrists and ophthalmologists. The goals should be to educate the patient regarding the diabetes disease process, nutritional management, physical activity, medications, glucose monitoring, and preventing and detecting complications. The success of diabetic teaching programs seems to be similar in the inpatient and ambulatory settings. A study by Muller and colleagues examined this question in a total of 140 patients with type 2 diabetes who received identical education programs in the 2 different settings. Patients were matched (70 ambulatory, 70 inpatient). There was no difference between the groups in regard to the improvements in HbA1c, body mass index, hypoglycemic episodes, and subsequent hospitalizations after 1 year. This suggests that education is equally effective in either setting. Furthermore, if the patient is hospitalized with other severe illnesses when diabetes is diagnosed, it may be prudent to delay diabetes education until the patient is stable and has left the hospital. Then he or she can focus full attention on the vitally important diabetes self-management education.
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