Glucose Intolerance Treatment & Management

Updated: Jul 08, 2020
  • Author: Samuel T Olatunbosun, MD, FACP, FACE; Chief Editor: George T Griffing, MD  more...
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Approach Considerations

Routine evaluation in an ambulatory setting is feasible for most patients. Patients with acute decompensation due to glucose intolerance or any related disorders may require inpatient care. A major goal in the management of glucose intolerance is glycemic control.

Of note is the novel treatment with DPP-4–resistant GLP-1 receptor agonists, such as exenatide and liraglutide, which are incretin mimetics, as well as with the DPP-4 inhibitors sitagliptin and vildagliptin. [48, 49, 50] Exenatide may be effective in preventing steroid-induced glucose intolerance through suppression. [51]

Both strategies have been successful in clinical studies. Liraglutide was approved by the FDA in January 2010 for monotherapy, as a second-line treatment and in combination with oral agents. The mechanisms of action of incretin mimetics include stimulation of insulin secretion in response to nutrient intake, inhibition of glucagon secretion, delay of gastric emptying, and induction of early satiety. Other benefits include preservation of beta cell mass and improvement of secretory function. The advantages of the DPP-IV inhibitors include oral availability, good tolerability, and weight neutrality.

Amylin has several glucoregulatory effects that complement those of insulin in postprandial glucose regulation; thus, mealtime amylin administration may be adjunctive to mealtime insulin replacement and may facilitate improvement of postprandial and overall glycemic control in patients with type 1 or type 2 diabetes. Naturally occurring human amylin is unsuitable for clinical use because of several physicochemical properties, however; pramlintide acetate contains an amylin analogue without those limitations. [52, 53, 54, 55, 56]

All patients with type 1 diabetes are insulin-dependent. Treatment of severe hyperglycemia during acute decompensation in a patient with type 2 diabetes may reverse the state of glucose toxicity, further improving secretory function of beta cells in the pancreas. Type 2 diabetes can be treated effectively with oral hypoglycemic drugs, with or without the addition of insulin. The natural history of type 2 diabetes is that of progressive beta-cell deterioration, secondary failure of oral agents, and the subsequent need for insulin therapy.

Gestational diabetes mellitus is treated with insulin and/or with lifestyle change. Oral agents are contraindicated in pregnancy.

With regard to the management of impaired glucose tolerance, the current approach is aggressive lifestyle modification. The results of the Diabetes Prevention Program showed that metformin therapy and intensive lifestyle intervention reduced the risk of developing type 1 and type 2 diabetes by 31% and 58%, respectively, compared with placebo in individuals with impaired glucose tolerance. [57] The Study to Prevent Non-Insulin–Dependent Diabetes Mellitus Trial demonstrated a 25% relative risk reduction in the development of diabetes, and an associated reduction in hypertension (34%) and cardiovascular events (49%). [58]

Orlistat may be beneficial in the context of obesity. [59]

Medical nutritional therapy should be guided by the American Dietetic Association recommendations and individualized by weight and height, level of physical activity, and requirements for calories and nutrients. [60]  A high level of physical activity is desirable, as appropriate to the patient's ability and general health. Most patients benefit from carefully planned exercise programs tailored to individual needs. [61]

Long-term monitoring of affected patients includes ensuring medication compliance, identifying adverse effects, blood glucose and HbA1c monitoring, dietary consultations and measures, and exercise management.

For more information, see Diabetes Mellitus, Type 1 and Diabetes Mellitus, Type 2.


Lifestyle Modification

Intensive lifestyle modification has been shown to effectively delay or prevent diabetes in a cost-effective manner. [59, 62, 63] Nonpharmacologic therapy and lifestyle modification include the following:

  • Diet 

  • Exercise

  • Counseling related to smoking cessation and alcohol intake

  • Reversing drug-related, iatrogenic causation of glucose intolerance

  • Substituting or adding agents that do not adversely affect glucose tolerance; reducing dosage of offending drugs

2018 USDHHS physical activity guidelines

The guidelines on physical activity were released in November 2018 by the Physical Activity Guidelines Advisory Committee of the US Department of Health and Human Services (USDHHS). [64, 65]

Age- and condition-related recommendations

Children aged 3-5 years: Should be physically active throughout the day to enhance growth and development.

Children aged 6-17 years: Sixty minutes or more of moderate-to-vigorous physical activity per day.

Adults: At least 150-300 minutes per week of moderate-intensity aerobic physical activity, OR  75-150 minutes per week of vigorous-intensity aerobic physical activity, OR an equivalent combination of moderate- and vigorous-intensity aerobic activity; muscle-strengthening activities should be performed on two or more days per week.

Older adults: Multicomponent physical activity to include balance training, aerobic activity, and muscle-strengthening activity.

Pregnant and postpartum women: At least 150 minutes of moderate-intensity aerobic activity weekly.

Adults with chronic conditions or disabilities who are able: Follow key guidelines and perform both aerobic and muscle-strengthening activities.

Sleep, daily functioning, and mental health

Strong evidence demonstrates that moderate-to-vigorous physical activity improves sleep quality by decreasing the time it takes to fall asleep; it can also increase deep-sleep time and decrease daytime sleepiness.

Single episodes of physical activity promote improvements in executive function, to include organization of daily activities and future planning. Cognition (ie, memory, processing speed, attention, academic performance) also can be improved with physical exercise.

Regular physical activity reduces the risk of clinical depression, as well as reducing depressive symptoms and symptoms of anxiety.

Strong evidence demonstrates regular physical activity improves perceived quality of life.

Risk of diseases and conditions

Regular physical activity minimizes excessive weight gain, helps maintain weight within a healthy range, improves bone health, and prevents obesity, even in children as young as 3-5 years.

In pregnant women, physical activity helps reduce excessive weight gain in pregnancy and helps reduce the risk of developing gestational diabetes and postpartum depression.

Regular physical activity has been shown to improve cognitive function and to reduce the risk of dementia; falls and fall-related injuries; and cancers of the breast, esophagus, colon, bladder, lung, endometrium, kidney, and stomach. It also helps retard the progression of osteoarthritis, type 2 diabetes, and hypertension.

Promotion of physical activity

School- and community-based programs can be effective.

Environmental and policy changes should improve access to physical activity and support of physical activity behavior.

Information and technology should be used to promote physical activity, to include activity monitors (eg, wearable devices), smartphone apps, computer-tailored printed material, and Internet-based programs for self-monitoring, message delivery, and support.


Pharmacologic Therapy

Pharmacologic therapy may be required in the following situations: [66]

  • Fasting glucose more than 126 mg/dL, postprandial glucose more than 160 mg/dL, or glycosylated hemoglobin (HbA1c) more than 7%

  • Hyperglycemia (a significant risk factor in development of vascular complications)

In addition to lifestyle counseling, metformin therapy for prevention of type 2 diabetes should be considered in those with prediabetes, especially for those with a body mass index (BMI) above 35 kg/m2, those younger than 60 years, women with prior gestational diabetes, and/or those with rising HBA1C despite lifestyle intervention. [4]

Note that long-term metformin use may be associated with biochemical vitamin B12 deficiency; thus, consider periodic measurement of vitamin B12 levels in patients receiving metformin, particularly those with anemia or peripheral neuropathy. [4]


Bariatric Surgery

Bariatric surgery should be considered in a patient with type 2 diabetes who has a BMI of more than 35 kg/m2, especially if glycemic control with lifestyle and pharmacotherapy is difficult. [1]  Surgically induced weight loss may result in improvements in insulin sensitivity and beta-cell function, as well as changes in gut hormones. [67, 68] Better diabetic control or complete resolution of the disease (64-93%) is the end result.

A bariatric procedure is not currently recommended in the management of IGT or IFG; however, glucose intolerance resolved in 99-100% of cases of patients who underwent bariatric surgery for a comorbid state that required such an intervention (eg, class 3 obesity).

Long-term support and medical monitoring are still important after a bariatric procedure. Various complications, including postprandial hyperinsulinemic hypoglycemia, have been reported following gastric bypass surgery.