• Diabetes
• • Sixth leading cause of death by disease 
  • Seventh leading cause of death in the United States 
  • Propensity for acute metabolic complications 
  • Leading cause of end-stage renal disease 
  • Leading cause of blindness 
  • Much higher risk of heart disease 
  • Higher risk of stroke 
  • High risk of neuropathy 
  • High risk of gangrene 
• Gestational diabetes mellitus
• • Increased risk of fetal and neonatal morbidity and mortality
  • Obstetric complications
  • Increased risk of obesity in offspring, glucose intolerance, and type 2 diabetes 
• Impaired glucose tolerance
• • Major risk factor for diabetes, with 20-50% progressing to diabetes within 10 years
  • Baseline plasma glucose is most consistent predictor of progression to diabetes
  • Rates of cardiovascular risk factors that are intermediate between those with normal glucose tolerance and those with diabetes
  • Increased risk of macrovascular complications (eg, coronary artery disease, gangrene, stroke)
  • Not clearly associated with microvascular complications (eg, nephropathy, retinopathy, neuropathy) 
• Impaired fasting glucose
• • Not associated with the same risk level as IGT
  • Risk of cardiovascular disease much lower in impaired fasting glucose

Race

• American Indians and certain Pacific Islanders have the highest risk of glucose intolerance.
• African Americans and Hispanics have higher rates of glucose intolerance than non-Hispanic whites.

Sex

• In the WHO global data, the prevalence ratio of diabetes between men and women varies markedly, with no consistent trend. However, impaired glucose tolerance is more common in women than in men.
• The relative difference in frequency between the sexes is probably related to the presence of underlying factors such as pregnancy and obesity rather than a sex-specific genetic tendency.

Age

• Type 1 diabetes occurs most commonly in children and adolescents but may occur in individuals of any age.
• Type 2 diabetes typically begins in middle life or later, usually after age 30 years; the prevalence rises with age.
• Maturity-onset diabetes of youth (MODY) can be expressed in childhood or early adolescence.

CLINICAL

Section 3 of 11  

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History

• Type 1 diabetes
• • The warning symptoms of type 1 diabetes include polyuria, polydipsia, and polyphagia due to hyperglycemia.
  • Patients may present with unexplained weight loss and easy fatigability that result from reduced glucose use and increased catabolism.
  • Irritability, drowsiness, and loss of consciousness may occur, especially as ketoacidosis develops. The temporal profile is consequent to progression of the metabolic derangement, which is characterized by dehydration, electrolyte abnormalities, osmolality, and acid-base disturbances.
  • After presentation with ketoacidosis, a patient may briefly revert to normoglycemia without requiring therapy, (ie, the honeymoon remission).
• Type 2 diabetes
• • Patients with type 2 diabetes may have any of the symptoms described under type 1 diabetes but often are asymptomatic.
  • Hyperosmolar nonketotic coma, which may complicate type 2 diabetes mellitus, is characterized by severe dehydration secondary to osmotic diuresis from hyperglycemia.
  • Ketoacidosis, although uncommon, may also occur in type 2 diabetes.
  • Antecedent history in patients with type 2 diabetes includes frequent or recurrent infections, poor wound healing, blurring of vision, and numbness or tingling sensations in the extremities.
• Gestational diabetes mellitus: This is typically detected during routine screening of pregnant women for glucose intolerance. Any degree of glucose intolerance with onset or recognition during gestation places a patient in the category of gestational diabetes mellitus.
• Impaired glucose tolerance (IGT) and impaired fasting glucose
• • Patients with impaired glucose homeostasis are generally asymptomatic.
  • Features of related risk factors for cardiovascular disease may be present, even with a mild degree of hyperglycemia. They include a history of hypertension; a history of obesity; a history of dyslipidemia; and a history of macrovascular disease such as stroke, coronary disease, or peripheral vascular disease.
  • In most cases of impaired glucose tolerance and impaired fasting glucose, the presence of one or more cardiovascular risk factors actually triggers a screening test for disorders of glucose tolerance.
• Glucose intolerance: Diagnosis of glucose intolerance may also be coincidental in patients with various conditions that may be complicated with glucose intolerance. These conditions include liver cirrhosis, end-stage renal disease, and some of the rare genetic disorders.

Physical

• Acute presentation
• • Overt hyperglycemia that has progressed to diabetes, if left untreated, may result in signs of dehydration. Hypotension and other features of hemodynamic decompensation occur with worsening hyperglycemia.
  • Other clinical features, such as Kussmaul respiration and altered level of consciousness due to metabolic derangement, are commonly observed during acute deterioration.
  • Evidence of a precipitating factor, such as fever from an infectious process, may be present and should always be sought.
• Routine evaluation
• • In routine evaluation of patients with glucose intolerance, weight, height, waist, and hip measurements are recommended. The aim is to determine the body mass index (BMI), the risk level, and the presence of truncal obesity. In type 2 diabetes, 60-90% of the patients are obese. A patient may have central adiposity in spite of a normal BMI. Skin-fold thickness measurement may also be useful in determining regional fat distribution, although it is not often accurate or reproducible.
  • Peripheral stigmata of lipid abnormalities and atherosclerosis, such as premature arcus cornealis, xanthelasma, eruptive (skin) xanthomata, tendon xanthomata, and lipemia retinalis, may be found in some patients.
  • Blood pressure measurement: Hypertension is a frequent component of the dysmetabolic syndrome. Hypertension is 1.5-2 times more common in individuals with diabetes than in matched individuals without diabetes. Approximately 40% of individuals with hypertension have impaired glucose tolerance.
• Thorough evaluation: A thorough evaluation of the various systems and organs is pertinent.
• • Eye examination: Ocular manifestations such as pupillary abnormalities, cataract, refractory errors, retinopathy, and other changes may be found in some patients with diabetes; these manifestations result mainly from chronic uncontrolled hyperglycemia.
  • Neurologic examination: Muscle wasting, sensory abnormalities, and other various features of neuropathy are also characteristic of many patients with diabetes who have chronic complications.
• Related diseases: Specific phenotypic characteristics are found in certain conditions, especially the genetic syndromes.
• • Type A insulin resistance: In addition to glucose intolerance, patients with type A insulin resistance (absent or dysfunctional insulin receptor) may have certain clinical features such as (1) acanthosis nigricans, which is hyperpigmentation and skin thickening of flexural areas, or (2) features of hyperandrogenism, of which some variants may be characterized by thin or muscular body habitus or acral enlargement (pseudoacromegaly).
  • Type B insulin resistance: Due to autoantibodies to the insulin receptor, this resistance commonly manifests as symptomatic diabetes mellitus; ketoacidosis is unusual. Other genetic syndromes associated with insulin resistance include leprechaunism (abnormal facies, growth retardation) and lipodystrophic states (diverse phenotypic manifestations).
  • Internal organ diseases: Other patients may have physical findings that are characteristic of certain internal organ diseases, in which glucose intolerance is only part of the spectrum of metabolic derangement that complicates these conditions. In cirrhosis, the liver may be normal, enlarged, or shrunken, depending on the stage of the disease. Other clinical features of portal hypertension and liver cell failure are often present. In cases of uremia, the various systemic changes, with the wide range of external manifestations that occur in the late phases of renal failure, are generally evident.

Causes

• Genetic defects of beta cell function include the following:
• • Mutation on chromosome 12, the hepatocyte nuclear factor (HNF-1) alpha - MODY3
  • Mutation on the chromosome 7p, the glucokinase gene - MODY2
  • Mutation on chromosome 20, HNF-4 alpha - MODY1
  • Point mutations in mitochondrial DNA
  • Others
• Defects in insulin action include the following:
• • Structure and function of insulin receptor - Postreceptor signal transduction pathways
  • Type A insulin resistance
  • Leprechaunism
  • Rabson-Mendenhall syndrome
  • Lipoatrophic diabetes
  • Others
• Diseases of exocrine pancreas include the following (Note that the category malnutrition-related diabetes has been eliminated because of lack of evidence of the association of protein deficiency with direct causation of diabetes, while fibrocalculous pancreatopathy was reclassified as a disease of exocrine pancreas.):
• • Pancreatitis
  • Trauma
  • Infection
  • Pancreatectomy
  • Pancreatic cancer
  • Cystic fibrosis
  • Hemochromatosis
  • Fibrocalculous pancreatopathy 
• Endocrine diseases associated with excess production of insulin antagonists include the following:
• • Acromegaly
  • Cushing syndrome
  • Glucagonoma
  • Pheochromocytoma
  • Hyperthyroidism
  • Somatostatinoma
  • Aldosteronoma
  • Others 
• Drugs or chemical agents with adverse effects include the following:
• • Thiazides
  • Diazoxide
  • Glucocorticoids
  • Oral contraceptives
  • Beta-adrenergic agonists
  • Nicotinic acid
  • Thyroid hormone
  • Pentamidine
  • Alpha interferon
  • Atypical antipsychotics especially clozapine and olanzapine
  • Vacor
  • Others 
• Infections associated with beta cell destruction include the following:
• • Rubella
  • Coxsackievirus B
  • Mumps
  • Cytomegalovirus
  • Adenovirus 
• Immune-mediated causes include the following:
• • Stiff man syndrome
  • Anti-insulin receptor abnormalities 
• Genetic syndromes include the following:
• • Down syndrome
  • Klinefelter syndrome
  • Turner syndrome
  • Wolfram syndrome
  • Friedreich ataxia 
• Pregnancy
• • Gestational diabetes mellitus
  • Risk of diabetes increases with parity
• Obesity
• • Powerful determinant of glucose intolerance in general population
  • Interaction of genetics and acquired factors such as physical inactivity and dietary habits
• Other causes of glucose intolerance include the following:
• • Liver disease (as in cirrhosis)
  • Renal failure

DIFFERENTIALS

Section 4 of 11  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

WORKUP

Section 5 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Lab Studies

• Plasma glucose measurement is used as a screening test and for confirmation of a previously detected abnormality of glucose tolerance. Fasting plasma glucose studies are the preferred diagnostic test of the ADA. A random plasma glucose measurement in the presence of classic diabetes symptoms is also acceptable.
• Oral glucose tolerance test
• • The standard oral glucose tolerance test (OGTT) involves measurement of plasma glucose concentration 2 hours after a 75-g oral glucose load. It is seldom used as a confirmatory test in the diagnosis of diabetes. However, OGTT may be helpful in situations in which fasting or random glucose results are equivocal. It is required in order to diagnose impaired glucose tolerance (IGT), although it is increasingly being reserved for research purposes.
  • A provisional diagnosis of diabetes must be confirmed on a subsequent day by any of the 3 methods, ie, fasting, casual, and OGTT.
  • The new ADA diagnostic criteria, with emphasis on fasting plasma glucose, facilitates the screening of individuals with undiagnosed diabetes, but the criteria help identify fewer people with diabetes when compared with OGTT.
  • The new ADA diagnostic criteria include the following:
  • • Normal glucose homeostasis - Fasting plasma glucose (FPG) level of less than 100 mg/dL and 2-hour OGTT result of less than 140 mg/dL after a 75-g oral glucose load
    • Impaired fasting glucose - Fasting plasma glucose level of 100 mg/dL or greater but less than 126 mg/dL, based on ADA criteria (The cutpoint for impaired fasting glucose levels was recently reduced from 110 mg/dL by the ADA with the aim of identifying more individuals who are at risk of developing diabetes.) 
    • Impaired glucose tolerance - Two-hour OGTT result of 140 mg/dL or greater but less than 200 mg/dL
    • Diabetes mellitus - (1) FPG level of 126 mg/dL or greater and a casual plasma glucose level of 200 mg/dL or greater, (2) a casual plasma glucose level of 200 mg/dL or greater on 2 occasions, or (3) the classic symptoms plus a 2-hour OGTT result of 200 mg/dL or greater
    • Gestational diabetes mellitus is defined as any degree of glucose intolerance with onset or first recognition during pregnancy. In the United States, the most popular screening test for gestational diabetes mellitus is a 1-hour plasma glucose measurement after a 50-g oral glucose load followed by (if necessary) 3-hour diagnostic testing using a 100-g load. The WHO-recommended procedure using a 75-gram oral glucose load is used in many parts of the world.  
• Screening tests for type 2 diabetes should be considered at 3-year intervals in all individuals older than 45 years, particularly if the body mass index (BMI) is 25 kg/m² or higher. Testing is indicated at a younger age or more frequently in individuals who are overweight (BMI ³25 kg/m²) and have additional risk factors, including the following:
• • Habitual physical inactivity
  • First-degree relation to a person with diabetes 
  • High-risk ethnic background (eg, Hispanic, American Indian, Asian American, African American, Pacific Islander)
  • Delivery of a large baby for gestational age (baby >9 lb) or history of gestational diabetes mellitus 
  • Hypertension (blood pressure ³140/90 mm Hg)
  • High-density lipoprotein cholesterol level of 35 mg/dL or less,  triglyceride level of 250 mg/dL or more, or both 
  • Polycystic ovary syndrome (PCOS) 
  • Impaired glucose tolerance or impaired fasting glucose as determined with previous testing 
  • Other clinical conditions associated with insulin resistance (eg,  acanthosis nigricans)
  • History of vascular disease 
• Urinalysis: Ketonuria and massive glycosuria are indicators of acute decompensation. Significant proteinuria may be present in patients with diabetic nephropathy. Abnormalities are found in specific gravity, and pH can be found in uremia.
• Urine microalbumin is a marker of early renal impairment and endothelial dysfunction.
• Glycated hemoglobin is not recommended as a diagnostic tool. It serves as an index of severity of hyperglycemia over 6-8 weeks preceding measurement. This is highly specific as evidence of chronic hyperglycemia. It is a predictor of chronic complications.
• Serum electrolytes, BUN, creatinine, uric acid, and blood gases: During acute decompensation, metabolic derangement from loss of water, sodium, potassium, other electrolytes, anion gap, and osmolality abnormalities are very common. Normal renal and hepatic function must be confirmed before therapy is started with some oral antidiabetic agents.
• Liver function tests: Assess baseline liver function to exclude hepatic disease prior to commencing certain antihyperglycemic agents (eg, biguanides and thiazolidinediones). Periodic measurements are required during treatment with thiazolidinediones. Liver cirrhosis is a cause of glucose intolerance.
• Lipid profile: An increased triglyceride level may be present. This is often a reflection of poor glycemic control and may normalize upon attainment of euglycemia. Other lipid abnormalities, such as increased total cholesterol and low-density lipoprotein levels, are commonly found.
• CBC count: Increased white blood cell count is common during acute infection. Ketoacidosis also is a cause of leukocytosis.
• C-peptide: An undetectable plasma level indicates type 1 diabetes (in the absence of hypoglycemia). C-peptide profiling may also be helpful in deciding treatment in some cases of type 2 diabetes. It is not routinely used in clinical practice.
• Plasma plasminogen activator inhibitor type 1: Increased levels of plasma plasminogen activator inhibitor type 1, a marker of impaired fibrinolysis, are frequently found in patients with glucose intolerance and are a correlate of insulin resistance syndrome.
• Homocysteine: An increased plasma homocysteine level is a risk factor for atherosclerosis. This should be measured in selected patients.

Other Tests

• ECG and other cardiac workup
  
  
  • Perform electrocardiography and other tests depending on the patient's cardiovascular risk profile.
  • Features of left ventricular hypertrophy, cardiomegaly, or both are common in patients with hypertension.
  • Low-risk patients may have normal test results, whereas other patients with significant cardiovascular disease may show evidence of ischemia with appropriate cardiac testing.

TREATMENT

Section 6 of 11  

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Medical Care

Routine evaluation in an ambulatory setting is feasible for most patients. Patients with acute decompensation due to glucose intolerance or to any of the related disorders may require inpatient care. See Consultations for other specialists who the patient may benefit from consulting.

A major goal in the management of glucose intolerance is glycemic control.

• Intensive lifestyle modification has been shown to effectively delay or prevent diabetes in a cost-effective manner.² Nonpharmacologic therapy and lifestyle modification include the following:
• • Diet
  • Exercise
  • Counseling for smoking cessation and counseling regarding alcohol use
  • Reversal of drug-related iatrogenic causation of glucose intolerance
  • Substitution or addition of agent or agents that do not adversely affect glucose tolerance or reduction of the dosage of the offending drug
• Pharmacologic therapy may be required in the following situations:³
• • Fasting glucose level is greater than 126 mg/dL, postprandial glucose level is greater than 160 mg/dL, or glycosylated hemoglobin (HbA1C) level is greater than 7%
  • Hyperglycemia (significant risk factor in the development of vascular complications)

Consultations

• Endocrinologist
• Dietitian
• Cardiologist, ophthalmologist, and nephrologist, depending on the presence of other related disorders and predominant pathology

Diet

Medical nutrition therapy should be guided by the ADA recommendations and individualized based on weight and height, level of physical activity, and requirements for calories and nutrients.

Activity

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.

MEDICATION

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Oral antidiabetic agents can be classified into functional categories, as follows:

• Secretagogues (eg, sulfonylureas, meglitinides), which stimulate insulin release
• Insulin sensitizers (eg, biguanides, thiazolidinediones), which reduce insulin resistance
• Medications that slow the digestive/absorptive process (eg, alpha-glucosidase inhibitors)

Of note is a novel treatment with dipeptidyl peptidase-4 (DPP-4)–resistant GLP-1 receptor agonists, such as exenatide and liraglutide, which are incretin mimetics; and DPP-4 inhibitors vildagliptin (LAF237; Novartis Pharmaceuticals) and sitagliptin (MK-0431; Merck & Co), which are currently in the late stage of clinical development. Both strategies have been successful in clinical studies. The action mechanisms 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 and type 2 diabetes. However, naturally occurring human amylin is unsuitable for clinical use because of several physicochemical properties; pramlintide acetate contains an amylin analogue without those limitations.

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, lifestyle change, or both. Oral agents are contraindicated in pregnancy.

In regard to the management of impaired glucose tolerance the current approach is aggressive lifestyle modifications. The results of the Diabetes Prevention Program (DPP) showed that both metformin therapy and intensive lifestyle intervention reduced the risk of developing type diabetes by 31% and 58% respectively,  compared with placebo, in individuals with impaired glucose tolerance. The STOP-NIDDM (The Study to Prevent Non-Insulin Dependent Diabetes Mellitus) Trial demonstrated a 25% relative risk reduction in the development of diabetes, and also associated reduction in hypertension (34%) and cardiovascular events (49%). Orlistat may be beneficial in the context of obesity.

Drug Category: Sulfonylureas

Chlorpropamide and tolbutamide (first-generation) and glipizide, glyburide, and glimepiride (second-generation) are secretagogues (ie, medications that stimulate insulin secretion).

Drug Category: Meglitinides

These agents stimulate insulin secretion from pancreatic cells.

Drug Category: Antidiabetic agents, biguanides

These agents improve peripheral glucose uptake and utilization.

Drug Category: Thiazolidinediones

These agents stimulate peripheral use of glucose as stimulated by insulin. Rosiglitazone and pioglitazone are commonly used.

The US Food and Drug Administration issued an alert on May 21, 2007 to patients and health care professionals of rosiglitazone potentially causing an increased risk of myocardial infarction (MI) and heart-related deaths following the online publication of a meta-analysis. Rosiglitazone is an antidiabetic agent (thiazolidinedione derivative) that improves glycemic control by improving insulin sensitivity.

The drug is highly selective and a potent agonist for peroxisome proliferator-activated receptor-gamma (PPAR-gamma). Activation of PPAR-gamma receptors regulates insulin-responsive gene transcription involved in glucose production, transport, and utilization, thereby reducing blood glucose concentrations and reducing hyperinsulinemia. Potent PPAR-gamma agonists have been shown to increase the incidence of edema. A large scale phase III trial (RECORD) is currently underway that is specifically designed to study cardiovascular outcomes of rosiglitazone.

For more information, see FDA’s Safety Alert on Avandia. The online published meta-analysis entitled Effect of “Rosiglitazone on the Risk of Myocardial Infarction and Death from Cardiovascular Causes” can be viewed at The New England Journal of Medicine. Additionally, responses to the controversy can be viewed at the Heartwire news (the heart.org from WebMD) including the following articles: 1) Rosiglitazone increases MI and CV death in meta-analysis and 2) The rosiglitazone aftermath: Legitimate concerns or hype?

Drug Category: Alpha-glucosidase inhibitors

These agents include acarbose and miglitol, which are medications that slow the digestive and absorptive process.

Drug Category: Antidiabetic agents, insulins

Insulin is used as hormone replacement.

Drug Category: Incretin mimetics

This new class of drugs broadens the armamentarium of antidiabetic medications. Exenatide and liraglutide are DPP-4–resistant GLP-1 receptor agonists or analogues. As incretin mimetics, they enhance insulin secretion, suppression of glucagon secretion, and slowing of gastric emptying. Exenatide was recently approved by the US Food and Drug Administration (FDA) as adjunctive therapy in patients who have not achieved adequate control with metformin or sulfonylurea; exenatide has been available since June 2005.

Drug Category: Amylin analogue

Pramlintide is an amylinomimetic agent that modulates gastric emptying, prevents postprandial increases in plasma glucagon, and promotes satiety, leading to decreased caloric intake and potential weight loss.

Although naturally-occurring human amylin is unsuitable for clinical use because of several physicochemical properties (eg, poor solubility; self-aggregation; formation of b-pleated sheets, amyloid fibrils, amyloid plaques), the selective substitution of the amino acid proline for Ala25, Ser28, and Ser29 addresses the suboptimal physicochemical properties of human amylin while preserving the important metabolic actions. Pramlintide acetate injection, which contains this amylin analogue, is a sterile, clear, colorless, aqueous solution that also contains mannitol for isotonicity and the preservative m-cresol.

FOLLOW-UP

Section 8 of 11  

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Further Inpatient Care

• Admit for treatment and close monitoring during severe acute decompensation.

Further Outpatient Care

• Monitoring of medication compliance and adverse effects
• Blood glucose and HbA1C monitoring
• Dietary consultation
• Dietary measures and exercise

In/Out Patient Meds

• Medications include sulfonylureas, meglitinides, biguanides and thiazolidinediones, alpha-glucosidase inhibitors, and insulin preparations, sometimes in combination.
• Carefully select medications that are beneficial in the context of comorbid states.

Transfer

• Transfer to a specialist for further evaluation and treatment if specific problems cannot be managed effectively at the primary care level or in the event of worsening of glucose intolerance in spite of best efforts to control it.

Deterrence/Prevention

• Avoid dietary indiscretion.
• Avoid physical inactivity.
• Quit or avoid smoking.
• Avoid ethanol abuse.

Complications

• Coronary artery disease (impaired glucose tolerance [IGT] and diabetes)
• Peripheral vascular disease (impaired glucose tolerance and diabetes)
• Stroke (impaired glucose tolerance and diabetes)
• Nephropathy (diabetes)
• Retinopathy (diabetes)
• Neuropathy (diabetes)
• Acute metabolic complications (diabetes)

Prognosis

• Impaired glucose tolerance is a risk factor for type 2 diabetes, with 20-50% of the individuals developing type 2 diabetes over 10 years. Approximately one third revert to normal glucose tolerance, while others persistently demonstrate impaired glucose tolerance as determined by oral glucose tolerance testing (OGTT).
• For gestational diabetes mellitus, reclassification is performed 6 weeks or longer postpartum. In most patients with gestational diabetes mellitus, glucose tolerance becomes normal after delivery. However, lifetime risk for impaired glucose tolerance and diabetes is increased substantially in these women.

Patient Education

• Educate patients on the disease, treatment, monitoring, complications, and primary and secondary preventive measures.
• Educate family members on various issues, including management of hypoglycemia.
• For excellent patient education resources, visit eMedicine's Diabetes Center. Also, see eMedicine's patient education articles Diabetes and Diabetic Eye Disease.

MISCELLANEOUS

Section 9 of 11  

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• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Medical/Legal Pitfalls

• Failure to recognize an association with major medical disorders such as hypertension, dyslipidemia, and coronary artery disease
• Failure to treat comorbid conditions
• Failure to inform the patient of potentially serious adverse effects that may occur with the use of some antihyperglycemic agents
• Failure to inform the patient of the possibility of progression of disease and development of complications

Special Concerns

• Increased glucose tolerance (IGT) and impaired fasting glucose do not imply normality, but they do not carry the stigma and connotations of the term diabetes.

MULTIMEDIA

Section 10 of 11  

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• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• Multimedia
• References

Media file 1:  Etiologic types and stages of the major disorders of glucose tolerance.
	View Full Size Image
Media type:  Graph

REFERENCES

Section 11 of 11

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• Follow-up
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• References

1. Buchanan TA, Xiang AH. Gestational diabetes mellitus. J Clin Invest. Mar 2005;115(3):485-91. [Medline].
2. Bourn DM, Mann JI, McSkimming BJ, Waldron MA, Wishart JD. Impaired glucose tolerance and NIDDM: does a lifestyle intervention program have an effect?. Diabetes Care. Nov 1994;17(11):1311-9. [Medline].
3. DeFronzo RA. Pharmacologic therapy for type 2 diabetes mellitus. Ann Intern Med. 1999;131(4):281-303. [Medline].
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5. Ahren B, Pacini G. Islet adaptation to insulin resistance: mechanisms and implications for intervention. Diabetes Obes Metab. 7(1):2-8.
6. Ahren B, Schmitz O. GLP-1 receptor agonists and DPP-4 inhibitors in the treatment of type 2 diabetes. Horm Metab Res. 36(11-12):867-76.
7. Alberti KG. Impaired glucose tolerance: what are the clinical implications?. Diabetes Res Clin Pract. 1998;40 Suppl:S3-8. [Medline].
8. American Diabetes Association. Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. Jan 2005;28(suppl_1):S37-S42. [Medline].
9. American Diabetes Association. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care. 1997;20(7):1183-97. [Medline].
10. Blake DR, Meigs JB, Muller DC, Najjar SS, Andres R, Nathan DM. Impaired glucose tolerance, but not impaired fasting glucose, is associated with increased levels of coronary heart disease risk factors: results from the Baltimore Longitudinal Study on Aging. Diabetes. Aug 2004;53(8):2095-100. [Medline].
11. Ceriello A, Piconi L, Quagliaro L, et al. Effects of pramlintide on postprandial glucose excursions and measures of oxidative stress in patients with type 1 diabetes. Diabetes Care. Mar 2005;28(3):632-7. [Medline].
12. Chiasson JL. Acarbose for the prevention of diabetes, hypertension, and cardiovascular disease in subjects with impaired glucose tolerance: the Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP-NIDDM) Trial. Endocr Pract. Jan-Feb 2006;12 Suppl 1:25-30.
13. Dagogo-Jack S, Santiago JV. Pathophysiology of type 2 diabetes and modes of action of therapeutic interventions. Arch Intern Med. Sep 8 1997;157(16):1802-17. [Medline].
14. DeFronzo RA. Pathogenesis of type 2 diabetes mellitus. Med Clin North Am. Jul 2004;88(4):787-835, ix. [Medline].
15. Diamant M, Bunck MC, Heine RJ. [Analogs of glucagon-like peptide-1 (GLP-1): an old concept as a new treatment of patients with diabetes mellitus type 2]. Ned Tijdschr Geneeskd. Sep 25 2004;148(39):1912-7. [Medline].
16. Einhorn D, Reaven GM, Cobin RH, et al. American College of Endocrinology position statement on the insulin resistance syndrome. Endocr Pract. May-Jun 2003;9(3):237-52. [Medline].
17. Festa A, D'Agostino R Jr, Hanley AJ, Karter AJ, Saad MF, Haffner SM. Differences in insulin resistance in nondiabetic subjects with isolated impaired glucose tolerance or isolated impaired fasting glucose. Diabetes. Jun 2004;53(6):1549-55.
18. Flier JS. Syndromes of insulin resistance. In: Becker KL, ed. Principles and Practice of Endocrinology and Metabolism. 2nd ed. Philadelphia, Pa: Lippincott; 1995:. 1249-59.
19. Gerich JE. Postprandial hyperglycemia and cardiovascular disease. Endocr Pract. Jan-Feb 2006;12 Suppl 1:47-51.
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