eMedicine Specialties > Endocrinology > Diabetes Mellitus

Diabetes Mellitus, Type 2

Author: Kenneth Patrick L Ligaray, MD, Fellow, Department of Endocrinology, Diabetes and Metabolism, St Louis University
Coauthor(s): William L Isley, MD, Senior Associate Consultant, Associate Professor of Medicine, Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic of Rochester
Contributor Information and Disclosures

Updated: Oct 28, 2009

Introduction

Background

Type 2 diabetes mellitus is a group of disorders characterized by hyperglycemia and associated with microvascular (ie, retinal, renal, possibly neuropathic), macrovascular (ie, coronary, peripheral vascular), and neuropathic (ie, autonomic, peripheral) complications. Unlike patients with type 1 diabetes mellitus, patients with type 2 are not absolutely dependent upon insulin for life, even though many of them are ultimately treated with insulin. (See images below and Images 5, 11.)

Diagnostic criteria (American Diabetes Associatio...

Diagnostic criteria (American Diabetes Association) for diabetes mellitus type 2.

[ CLOSE WINDOW ]
Diagnostic criteria (American Diabetes Associatio...

Diagnostic criteria (American Diabetes Association) for diabetes mellitus type 2.


Treatment of type 2 diabetes mellitus.

Treatment of type 2 diabetes mellitus.

[ CLOSE WINDOW ]
Treatment of type 2 diabetes mellitus.

Treatment of type 2 diabetes mellitus.


Pathophysiology

Hyperglycemia results from lack of endogenous insulin, which is either absolute, as in type 1 diabetes mellitus, or relative, as in type 2 diabetes mellitus. Relative insulin deficiency usually occurs because of resistance to the actions of insulin in muscle, fat, and the liver and an inadequate response by the pancreatic beta cell. Insulin resistance, which has been attributed to elevated levels of free fatty acids in plasma,1  leads to decreased glucose transport in muscle, elevated hepatic glucose production, and increased breakdown of fat.

The genetics of type 2 diabetes are complex and not completely understood, but presumably this disease is related to multiple genes (with the exception of maturity-onset diabetes of the young [MODY]). Evidence supports inherited components for pancreatic beta-cell failure and insulin resistance. Considerable debate exists regarding the primary defect in type 2 diabetes mellitus. Most patients have insulin resistance and some degree of insulin deficiency. However, insulin resistance per se is not the sine qua non for type 2 diabetes mellitus because many people with insulin resistance (particularly those who are obese) do not develop glucose intolerance. Therefore, insulin deficiency is necessary for the development of hyperglycemia. Insulin concentrations may be high, yet inappropriately low for the level of glycemia.

MODY is associated with autosomal dominant inheritance and is characterized by onset in at least 1 family member younger than 25 years, absence of autoantibodies, correction of fasting hyperglycemia without insulin for at least 2 years, and absence of ketosis. At least 6 genetically different types of MODY have been described.2 Some patients ultimately require insulin to control glycemia. Variants in 2 of the genes associated with MODY (HNF-1alpha and, to a lesser extent, HNF-4alpha) have been shown to predict future type 2 diabetes.3

Presumably, the defects of type 2 diabetes mellitus occur when a diabetogenic lifestyle (ie, excessive caloric intake, inadequate caloric expenditure, obesity) is superimposed upon a susceptible genotype. The body mass index at which excess weight increases risk for diabetes varies with different racial groups. For example, compared with persons of European ancestry, persons of Asian ancestry are at increased risk for diabetes at lower levels of overweight.4   In addition, an in utero environment resulting in low birth weight may predispose some individuals to develop type 2 diabetes mellitus.5,6 A simplified scheme for the pathophysiology of abnormal glucose metabolism in type 2 diabetes mellitus is depicted in the image below (see also Image 1).

Simplified scheme for the pathophysiology of type...

Simplified scheme for the pathophysiology of type 2 diabetes mellitus.

[ CLOSE WINDOW ]
Simplified scheme for the pathophysiology of type...

Simplified scheme for the pathophysiology of type 2 diabetes mellitus.


Hyperglycemia appears to be the determinant of microvascular and metabolic complications. However, glycemia is much less related to macrovascular disease. Insulin resistance with concomitant lipid (ie, small dense low-density lipoprotein [LDL] particles, low high-density lipoprotein-cholesterol [HDL-C] levels, elevated triglyceride-rich remnant lipoproteins) and thrombotic (ie, elevated type-1 plasminogen activator inhibitor [PAI-1], elevated fibrinogen) abnormalities, as well as conventional atherosclerotic risk factors (eg, family history, smoking, hypertension, elevated low-density lipoprotein-cholesterol [LDL-C], low HDL-C), determine cardiovascular risk.

Increased cardiovascular risk appears to begin prior to the development of frank hyperglycemia, presumably because of the effects of insulin resistance. Stern in 19967 and Haffner and D'Agostino in 19998 developed the "ticking clock" hypothesis of complications, asserting that the clock starts ticking for microvascular risk at the onset of hyperglycemia, while the clock starts ticking for macrovascular risk at some antecedent point, presumably with the onset of insulin resistance.

Frequency

United States

In 2007, the estimated prevalence of diabetes in the United States was 7.8% (23.6 million people); almost one third of cases were undiagnosed.9 More than 90% of cases of diabetes are type 2 diabetes mellitus. With increasing obesity in the population, an older population, and an increase in the population of higher-risk minority groups (see Race), prevalence is increasing.

International

Type 2 diabetes mellitus is less common in non-Western countries where the diet contains fewer calories and caloric expenditure on a daily basis is higher. However, as people in these countries adopt Western lifestyles, weight gain and type 2 diabetes mellitus are becoming virtually epidemic.

Mortality/Morbidity

Diabetes mellitus is one of the leading causes of morbidity and mortality in the United States because of its role in the development of optic, renal, neuropathic, and cardiovascular disease. These complications, particularly cardiovascular disease (~50-75% of medical expenditures), are the major sources of expenses for patients with diabetes mellitus. Approximately two thirds of people with diabetes die from heart disease or stroke. Men with diabetes face a 2-fold increased risk for coronary heart disease, and women have a 3- to 4-fold increased risk. In 1994, 1 of every 7 health care dollars in the United States was spent on patients with diabetes mellitus. The 2002 estimate for direct medical costs due to diabetes in the United States was $92 billion, with another $40 billion in indirect costs. Approximately 20% of Medicare funds are spent on these patients.

  • Diabetes mellitus is the leading cause of blindness in working-age adults in the United States; diabetic retinopathy accounts for 12,000-24,000 newly blind persons every year.9 The National Eye Institute estimates that laser surgery and appropriate follow-up care can reduce the risk of blindness from diabetic retinopathy by 90%.10
  • Diabetes mellitus is the leading cause of end-stage renal disease (ESRD), accounting for 44% of new cases, according to the Centers for Disease Control and Prevention (CDC).11 In 2005, 46,739 people in the United States and Puerto Rico began renal replacement therapy, and 178,689 people with diabetes were on dialysis or had received a kidney transplant.9
  • Diabetes mellitus is the leading cause of nontraumatic lower limb amputations in the United States, with a 15- to 40-fold increase in risk over that of the nondiabetic population. In 2004, about 71,000 nontraumatic lower limb amputations were performed related to neuropathy and vasculopathy.9

Race

The prevalence of type 2 diabetes mellitus varies widely among various racial and ethnic groups. The image below shows data for various groups (see also Image 2). Type 2 diabetes mellitus is becoming virtually pandemic in some groups of Native Americans and Hispanic people. The risk of retinopathy and nephropathy appears to be greater in blacks, Native Americans, and Hispanics.

Prevalence of diabetes mellitus type 2 in various...

Prevalence of diabetes mellitus type 2 in various racial and ethnic groups in the United States (2007 estimates).

[ CLOSE WINDOW ]
Prevalence of diabetes mellitus type 2 in various...

Prevalence of diabetes mellitus type 2 in various racial and ethnic groups in the United States (2007 estimates).


Sex

Type 2 diabetes mellitus is slightly more common in older women than men.

Age

While type 2 diabetes mellitus traditionally has been thought to affect individuals older than 40 years, it is being recognized increasingly in younger persons, particularly in highly susceptible racial and ethnic groups and the obese. In some areas, more type 2 than type 1 diabetes mellitus is being diagnosed in prepubertal children, teenagers, and young adults. The prevalence of diabetes mellitus by age is shown in the image below (see also Image 3). Virtually all cases of diabetes mellitus in older individuals are type 2.

Prevalence of diabetes mellitus type 2 by age in ...

Prevalence of diabetes mellitus type 2 by age in the United States (2007 estimates).

[ CLOSE WINDOW ]
Prevalence of diabetes mellitus type 2 by age in ...

Prevalence of diabetes mellitus type 2 by age in the United States (2007 estimates).


Clinical

History

  • While a diagnosis of diabetes mellitus is readily entertained when a patient presents with classic symptoms (ie, polyuria, polydipsia, polyphagia, weight loss), most patients with type 2 diabetes mellitus are asymptomatic for years. Other symptoms that might suggest hyperglycemia include blurred vision, lower extremity paresthesias, or yeast infections, particularly balanitis in men. However, the asymptomatic state does not mean that hyperglycemia is not affecting the individual.
  • The possible presence of diabetes mellitus should be considered in obese patients, patients with a first-degree relative with type 2 diabetes mellitus, members of high-risk ethnic groups (ie, black, Hispanic, Native American, Asian American, Pacific Islander), women with a previous delivery of a large infant (>9 lb) or with a history of gestational diabetes mellitus, patients with hypertension, or patients with high triglycerides (>250 mg/dL) or low HDL-C (<35 mg/dL). While the United States Public Health Service and the American College of Physicians do not recommend routine screening for diabetes, targeted screening may be useful. For example, in one study of patients admitted to the hospital with acute coronary syndrome, none of whom were known to have diabetes, admission and fasting plasma glucose testing identified diabetes in 27%.12
  • Because polycystic ovary disease is an insulin-resistant state, screening these women may be warranted.
  • Whether at-risk persons should be screened for prediabetes is unclear at present. The therapy would generally be lifestyle changes to facilitate weight loss and improve cardiovascular fitness, and in virtually all cases, this would be the recommendation for such patients without a measured glucose value.

Physical

Early in the course of diabetes mellitus, the physical examination findings are likely to be unrevealing. However, ultimately, end-organ damage may be observed. Potential findings are listed in the image below (see also Image 4).

Possible physical examination findings in patient...

Possible physical examination findings in patients with type 2 diabetes mellitus.

[ CLOSE WINDOW ]
Possible physical examination findings in patient...

Possible physical examination findings in patients with type 2 diabetes mellitus.


Causes

  • Superimposition of caloric excess (typically, high intake and low expenditure) on a susceptible genotype appears to cause type 2 diabetes mellitus. A large, population-based, prospective study has shown that an energy-dense diet may be a risk factor for the development of diabetes that is independent of baseline obesity.13
  • Diabetes mellitus may be caused by other conditions. Secondary diabetes may occur in patients taking glucocorticoids or when patients have conditions that antagonize the actions of insulin (eg, Cushing syndrome, acromegaly, pheochromocytoma).

More on Diabetes Mellitus, Type 2

Overview: Diabetes Mellitus, Type 2
Differential Diagnoses & Workup: Diabetes Mellitus, Type 2
Treatment & Medication: Diabetes Mellitus, Type 2
Follow-up: Diabetes Mellitus, Type 2
Multimedia: Diabetes Mellitus, Type 2
References
Further Reading
[ CLOSE WINDOW ]

References

  1. Boden G. Fatty acids and insulin resistance. Diabetes Care. Apr 1996;19(4):394-5. [Medline].

  2. Gat-Yablonski G, Shalitin S, Phillip M. Maturity onset diabetes of the young--review. Pediatr Endocrinol Rev. Aug 2006;3 Suppl 3:514-20. [Medline].

  3. Holmkvist J, Almgren P, Lyssenko V, et al. Common variants in maturity-onset diabetes of the young genes and future risk of type 2 diabetes. Diabetes. Jun 2008;57(6):1738-44. [Medline]. [Full Text].

  4. Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies. Lancet. Jan 10 2004;363(9403):157-63. [Medline].

  5. Dabelea D, Pettitt DJ, Hanson RL, et al. Birth weight, type 2 diabetes, and insulin resistance in Pima Indian children and young adults. Diabetes Care. Jun 1999;22(6):944-50. [Medline]. [Full Text].

  6. Yarbrough DE, Barrett-Connor E, Kritz-Silverstein D. Birth weight, adult weight, and girth as predictors of the metabolic syndrome in postmenopausal women: the Rancho Bernardo Study. Diabetes Care. Oct 1998;21(10):1652-8. [Medline].

  7. Stern MP. Do non-insulin-dependent diabetes mellitus and cardiovascular disease share common antecedents?. Ann Intern Med. Jan 1 1996;124(1 Pt 2):110-6. [Medline].

  8. Haffner SM, D'Agostino R Jr, Mykkanen L, et al. Insulin sensitivity in subjects with type 2 diabetes. Relationship to cardiovascular risk factors: the Insulin Resistance Atherosclerosis Study. Diabetes Care. Apr 1999;22(4):562-8. [Medline]. [Full Text].

  9. National Institute of Diabetes and Digestive and Kidney Diseases. National Diabetes Statistics, 2007. National Diabetes Information Clearinghouse. Available at http://diabetes.niddk.nih.gov/DM/PUBS/statistics/. Accessed March 30, 2009.

  10. National Eye Institute. Diabetic Eye Disease FAQ: Prevention & Treatment. National Eye Institute. Available at http://www.nei.nih.gov/diabetes/content/english/faq2.asp. Accessed April 6, 2009.

  11. CDC. National Diabetes Fact Sheet, 2007. Centers for Disease Control and Prevention. Available at http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2007.pdf. Accessed April 10, 2009.

  12. [Best Evidence] Okosieme OE, Peter R, Usman M, et al. Can admission and fasting glucose reliably identify undiagnosed diabetes in patients with acute coronary syndrome?. Diabetes Care. Oct 2008;31(10):1955-9. [Medline]. [Full Text].

  13. [Best Evidence] Wang J, Luben R, Khaw KT, et al. Dietary energy density predicts the risk of incident type 2 diabetes: the European Prospective Investigation of Cancer (EPIC)-Norfolk Study. Diabetes Care. Nov 2008;31(11):2120-5. [Medline]. [Full Text].

  14. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care. Jan 2003;26 Suppl 1:S5-20. [Medline]. [Full Text].

  15. World Health Organization. Diabetes Mellitus: Report of WHO Study Group. Geneva: World Health Organization; 1985. Tech. Rep. Ser.

  16. International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care. Jun 5 2009;[Medline]. [Full Text].

  17. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. Sep 12 1998;352(9131):837-53. [Medline].

  18. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet. Sep 12 1998;352(9131):854-65. [Medline].

  19. UK Prospective Diabetes Study Group. Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39. BMJ. Sep 12 1998;317(7160):713-20. [Medline].

  20. Dluhy RG, McMahon GT. Intensive glycemic control in the ACCORD and ADVANCE trials. N Engl J Med. Jun 12 2008;358(24):2630-3. [Medline]. [Full Text].

  21. Skyler JS, Bergenstal R, Bonow RO, et al. Intensive glycemic control and the prevention of cardiovascular events: implications of the ACCORD, ADVANCE, and VA Diabetes Trials: a position statement of the American Diabetes Association and a Scientific Statement of the American College of Cardiology Foundation and the American Heart Association. J Am Coll Cardiol. Jan 20 2009;53(3):298-304. [Medline].

  22. Standards of medical care in diabetes--2008. Diabetes Care. Jan 2008;31 Suppl 1:S12-54. [Medline]. [Full Text].

  23. Queale WS, Seidler AJ, Brancati FL. Glycemic control and sliding scale insulin use in medical inpatients with diabetes mellitus. Arch Intern Med. Mar 10 1997;157(5):545-52. [Medline].

  24. Sawin CT. Action without benefit. The sliding scale of insulin use. Arch Intern Med. Mar 10 1997;157(5):489. [Medline].

  25. [Best Evidence] Wiener RS, Wiener DC, Larson RJ. Benefits and risks of tight glucose control in critically ill adults: a meta-analysis. JAMA. Aug 27 2008;300(8):933-44. [Medline]. [Full Text].

  26. Finfer S, Chittock DR, Su SY, et al. Intensive versus conventional glucose control in critically ill patients. N Engl J Med. Mar 26 2009;360(13):1283-97. [Medline].

  27. Malmberg K. Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus. DIGAMI (Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction) Study Group. BMJ. May 24 1997;314(7093):1512-5. [Medline]. [Full Text].

  28. Malmberg K, Ryden L, Wedel H, et al. Intense metabolic control by means of insulin in patients with diabetes mellitus and acute myocardial infarction (DIGAMI 2): effects on mortality and morbidity. Eur Heart J. Apr 2005;26(7):650-61. [Medline]. [Full Text].

  29. American Diabetes Association. Preconception care of women with diabetes. Diabetes Care. Jan 2000;23 Suppl 1:S65-8. [Medline].

  30. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ. Sep 12 1998;317(7160):703-13. [Medline].

  31. Hansson L, Zanchetti A, Carruthers SG, et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group. Lancet. Jun 13 1998;351(9118):1755-62. [Medline].

  32. American Diabetes Association. Management of dyslipidemia in adults with diabetes. Diabetes Care. Jan 2000;23 Suppl 1:S57-60. [Medline].

  33. [Best Evidence] Esposito K, Maiorino MI, Ciotola M, et al. Effects of a Mediterranean-style diet on the need for antihyperglycemic drug therapy in patients with newly diagnosed type 2 diabetes: a randomized trial. Ann Intern Med. Sep 1 2009;151(5):306-14. [Medline].

  34. [Best Evidence] Loimaala A, Groundstroem K, Rinne M, et al. Effect of long-term endurance and strength training on metabolic control and arterial elasticity in patients with type 2 diabetes mellitus. Am J Cardiol. Apr 1 2009;103(7):972-7. [Medline].

  35. Scarpello JH, Howlett HC. Metformin therapy and clinical uses. Diab Vasc Dis Res. Sep 2008;5(3):157-67. [Medline]. [Full Text].

  36. [Best Evidence] Bodmer M, Meier C, Krahenbuhl S, et al. Metformin, sulfonylureas, or other antidiabetes drugs and the risk of lactic acidosis or hypoglycemia: a nested case-control analysis. Diabetes Care. Nov 2008;31(11):2086-91. [Medline]. [Full Text].

  37. Turner RC, Cull CA, Frighi V. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group. JAMA. Jun 2 1999;281(21):2005-12. [Medline].

  38. UK Prospective Diabetes Study Group. UKPDS 28: a randomized trial of efficacy of early addition of metformin in sulfonylurea-treated type 2 diabetes. Diabetes Care. Jan 1998;21(1):87-92. [Medline].

  39. [Best Evidence] Kooy A, de Jager J, Lehert P, et al. Long-term effects of metformin on metabolism and microvascular and macrovascular disease in patients with type 2 diabetes mellitus. Arch Intern Med. Mar 23 2009;169(6):616-25. [Medline].

  40. [Best Evidence] Pradhan AD, Everett BM, Cook NR, et al. Effects of initiating insulin and metformin on glycemic control and inflammatory biomarkers among patients with type 2 diabetes: the LANCET randomized trial. JAMA. Sep 16 2009;302(11):1186-94. [Medline].

  41. Dormandy JA, Charbonnel B, Eckland DJ, et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet. Oct 8 2005;366(9493):1279-89. [Medline].

  42. [Best Evidence] Loke YK, Singh S, Furberg CD. Long-term use of thiazolidinediones and fractures in type 2 diabetes: a meta-analysis. CMAJ. Jan 6 2009;180(1):32-9. [Medline]. [Full Text].

  43. [Best Evidence] Drucker DJ, Buse JB, Taylor K, et al. Exenatide once weekly versus twice daily for the treatment of type 2 diabetes: a randomised, open-label, non-inferiority study. Lancet. Oct 4 2008;372(9645):1240-50. [Medline].

  44. [Best Evidence] Bunck MC, Diamant M, Corner A, et al. One-year treatment with exenatide improves beta-cell function, compared with insulin glargine, in metformin-treated type 2 diabetic patients: a randomized, controlled trial. Diabetes Care. May 2009;32(5):762-8. [Medline].

  45. Agency for Healthcare Research and Quality. Comparative Effectiveness, Safety, and Indications of Insulin Analogues in Premixed Formulations for Adults With Type 2 Diabetes. AHRQ: Agency for Healthcare Research and Quality. Available at http://effectivehealthcare.ahrq.gov/healthInfo.cfm?infotype=rr&ProcessID=18&Docid=108. Accessed April 13, 2009.

  46. US Food and Drug Administration. Early Communication About Safety of Lantus (Insulin Glargine). [Full Text].

  47. Agency for Healthcare Research and Quality. Comparative Effectiveness and Safety of Oral Diabetes Medications for Adults With Type 2 Diabetes. AHRQ: Agency for Healthcare Research and Quality. Available at http://effectivehealthcare.ahrq.gov/healthInfo.cfm?infotype=rr&ProcessID=6&DocID=40. Accessed January 27, 2009.

  48. [Best Evidence] Qayyum R, Bolen S, Maruthur N, et al. Systematic review: comparative effectiveness and safety of premixed insulin analogues in type 2 diabetes. Ann Intern Med. Oct 21 2008;149(8):549-59. [Medline]. [Full Text].

  49. [Best Evidence] Home PD, Pocock SJ, Beck-Nielsen H, et al. Rosiglitazone evaluated for cardiovascular outcomes in oral agent combination therapy for type 2 diabetes (RECORD): a multicentre, randomised, open-label trial. Lancet. Jun 20 2009;373(9681):2125-35. [Medline].

  50. Knowler WC, Barrett-Connor E, Fowler SE, et al. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. Feb 7 2002;346(6):393-403. [Medline]. [Full Text].

  51. Xiang AH, Hodis HN, Kawakubo M, et al. Effect of pioglitazone on progression of subclinical atherosclerosis in non-diabetic premenopausal Hispanic women with prior gestational diabetes. Atherosclerosis. Jul 2008;199(1):207-14. [Medline].

  52. Chiasson JL, Josse RG, Hunt JA, et al. The efficacy of acarbose in the treatment of patients with non-insulin-dependent diabetes mellitus. A multicenter controlled clinical trial. Ann Intern Med. Dec 15 1994;121(12):928-35. [Medline].

  53. DREAM (Diabetes REduction Assessment with ramipril and rosiglitazone Medication) Trial Investigators; Gerstein HC, Yusuf S, Bosch J, et al. Effect of rosiglitazone on the frequency of diabetes in patients with impaired glucose tolerance or impaired fasting glucose: a randomised controlled trial. Lancet. Sep 23 2006;368(9541):1096-105. [Medline].

  54. [Best Evidence] DREAM Trial Investigators; Bosch J, Yusuf S, Gerstein HC, Pogue J, Sheridan P, Dagenais G, et al. Effect of ramipril on the incidence of diabetes. N Engl J Med. Oct 12 2006;355(15):1551-62. [Medline].

  55. American Diabetes Association. Aspirin therapy in diabetes. Diabetes Care. Jan 2000;23 Suppl 1:S61-2. [Medline].

  56. [Best Evidence] Ogawa H, Nakayama M, Morimoto T, et al. Low-dose aspirin for primary prevention of atherosclerotic events in patients with type 2 diabetes: a randomized controlled trial. JAMA. Nov 12 2008;300(18):2134-41. [Medline].

  57. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. Nov 19 1994;344(8934):1383-9. [Medline].

  58. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. Jul 6 2002;360(9326):7-22. [Medline].

  59. Sever PS, Dahlof B, Poulter NR, et al. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial--Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet. Apr 5 2003;361(9364):1149-58. [Medline].

  60. Colhoun HM, Betteridge DJ, Durrington PN, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet. Aug 21-27 2004;364(9435):685-96. [Medline].

  61. Rubins HB, Robins SJ, Collins D, et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group. N Engl J Med. Aug 5 1999;341(6):410-8. [Medline].

  62. A randomized trial of therapies for type 2 diabetes and coronary artery disease. N Engl J Med. Jun 7 2009;[Medline]. [Full Text].

  63. [Best Evidence] Sjolie AK, Klein R, Porta M, et al. Effect of candesartan on progression and regression of retinopathy in type 2 diabetes (DIRECT-Protect 2): a randomised placebo-controlled trial. Lancet. Oct 18 2008;372(9647):1385-93. [Medline].

  64. Oshitari T, Asaumi N, Watanabe M, et al. Severe macular edema induced by pioglitazone in a patient with diabetic retinopathy: a case study. Vasc Health Risk Manag. 2008;4(5):1137-40. [Medline]. [Full Text].

  65. American Diabetes Association. Preventive foot care in people with diabetes. Diabetes Care. Jan 2000;23 Suppl 1:S55-6. [Medline].

  66. Food and Drug Administration. FDA Requires Boxed Warning and Risk Mitigation Strategy for Metoclopramide-Containing Drugs. U.S. Food and Drug Administration. Available at http://www.fda.gov/bbs/topics/NEWS/2009/NEW01963.html. Accessed April 9, 2009.

  67. [Best Evidence] Bell DS, Bakris GL, McGill JB. Comparison of carvedilol and metoprolol on serum lipid concentration in diabetic hypertensive patients. Diabetes Obes Metab. Mar 2009;11(3):234-8. [Medline].

  68. National High Blood Pressure Education Program. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. National Heart, Lung and Blood Institute. Available at http://www.nhlbi.nih.gov/guidelines/hypertension/jnc7full.pdf. Accessed April 9, 2009.

  69. [Best Evidence] Duke SA, Colagiuri S, Colagiuri R. Individual patient education for people with type 2 diabetes mellitus. Cochrane Database Syst Rev. Jan 21 2009;CD005268. [Medline].

  70. Abate N. Insulin resistance and obesity. The role of fat distribution pattern. Diabetes Care. Mar 1996;19(3):292-4. [Medline].

  71. Abbasi F, Kamath V, Rizvi AA, Carantoni M, Chen YD, Reaven GM. Results of a placebo-controlled study of the metabolic effects of the addition of metformin to sulfonylurea-treated patients. Evidence for a central role of adipose tissue. Diabetes Care. Dec 1997;20(12):1863-9. [Medline].

  72. Abraira C, Colwell J, Nuttall F, Sawin CT, Henderson W, Comstock JP, et al. Cardiovascular events and correlates in the Veterans Affairs Diabetes Feasibility Trial. Veterans Affairs Cooperative Study on Glycemic Control and Complications in Type II Diabetes. Arch Intern Med. Jan 27 1997;157(2):181-8. [Medline].

  73. Abraira C, Henderson WG, Colwell JA, Nuttall FQ, Comstock JP, Emanuele NV, et al. Response to intensive therapy steps and to glipizide dose in combination with insulin in type 2 diabetes. VA feasibility study on glycemic control and complications (VA CSDM). Diabetes Care. Apr 1998;21(4):574-9. [Medline]. [Full Text].

  74. Adler AI, Boyko EJ, Ahroni JH, Smith DG. Lower-extremity amputation in diabetes. The independent effects of peripheral vascular disease, sensory neuropathy, and foot ulcers. Diabetes Care. Jul 1999;22(7):1029-35. [Medline]. [Full Text].

  75. Adler AI, Neil HA, Manley SE, et al. Hyperglycemia and hyperinsulinemia at diagnosis of diabetes and their association with subsequent cardiovascular disease in the United Kingdom prospective diabetes study (UKPDS 47). Am Heart J. Nov 1999;138(5 Pt 1):S353-9. [Medline].

  76. Adler AI, Stratton IM, Neil HA, Yudkin JS, Matthews DR, Cull CA, et al. Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study. BMJ. Aug 12 2000;321(7258):412-9. [Medline]. [Full Text].

  77. Agurs-Collins TD, Kumanyika SK, Ten Have TR, Adams-Campbell LL. A randomized controlled trial of weight reduction and exercise for diabetes management in older African-American subjects. Diabetes Care. Oct 1997;20(10):1503-11. [Medline].

  78. Ahmad J, Siddiqui MA, Ahmad H. Effective postponement of diabetic nephropathy with enalapril in normotensive type 2 diabetic patients with microalbuminuria. Diabetes Care. Oct 1997;20(10):1576-81. [Medline].

  79. Ajani UA, Hennekens CH, Spelsberg A, Manson JE. Alcohol consumption and risk of type 2 diabetes mellitus among US male physicians. Arch Intern Med. Apr 10 2000;160(7):1025-30. [Medline].

  80. American Diabetes Association. Consensus Development Conference on Diabetic Foot Wound Care: 7-8 April 1999, Boston, Massachusetts. Diabetes Care. Aug 1999;22(8):1354-60. [Medline]. [Full Text].

  81. American Diabetes Association. Diabetes mellitus and exercise. Diabetes Care. Jan 2000;23 Suppl 1:S50-4. [Medline].

  82. American Diabetes Association. Diabetic nephropathy. Diabetes Care. Jan 2000;23 Suppl 1:S69-72. [Medline].

  83. American Diabetes Association. Diabetic retinopathy. Diabetes Care. Jan 2000;23 Suppl 1:S73-6. [Medline].

  84. American Diabetes Association. Implications of the Diabetes Control and Complications Trial. Diabetes Care. Jan 2000;23 Suppl 1:S24-6. [Medline].

  85. American Diabetes Association. Implications of the United Kingdom Prospective Diabetes Study. Diabetes Care. Jan 2000;23 Suppl 1:S27-31. [Medline].

  86. American Diabetes Association. Nutrition recommendations and principles for people with diabetes mellitus. Diabetes Care. Jan 2000;23 Suppl 1:S43-6. [Medline].

  87. American Diabetes Association. Smoking and diabetes. Diabetes Care. Jan 2000;23 Suppl 1:S63-4. [Medline].

  88. Anderson JH Jr, Brunelle RL, Keohane P, Koivisto VA, Trautmann ME, Vignati L, et al. Mealtime treatment with insulin analog improves postprandial hyperglycemia and hypoglycemia in patients with non-insulin-dependent diabetes mellitus. Multicenter Insulin Lispro Study Group. Arch Intern Med. Jun 9 1997;157(11):1249-55. [Medline].

  89. Aronson D, Rayfield EJ, Chesebro JH. Mechanisms determining course and outcome of diabetic patients who have had acute myocardial infarction. Ann Intern Med. Feb 15 1997;126(4):296-306. [Medline]. [Full Text].

  90. Aviles-Santa L, Sinding J, Raskin P. Effects of metformin in patients with poorly controlled, insulin-treated type 2 diabetes mellitus. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. Aug 3 1999;131(3):182-8. [Medline]. [Full Text].

  91. Bakris GL, Williams M, Dworkin L, Elliott WJ, Epstein M, Toto R, et al. Preserving renal function in adults with hypertension and diabetes: a consensus approach. National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group. Am J Kidney Dis. Sep 2000;36(3):646-61. [Medline].

  92. Balasubramanyam A, Zern JW, Hyman DJ, Pavlik V. New profiles of diabetic ketoacidosis: type 1 vs type 2 diabetes and the effect of ethnicity. Arch Intern Med. Oct 25 1999;159(19):2317-22. [Medline].

  93. Barker DJ. The fetal origins of type 2 diabetes mellitus. Ann Intern Med. Feb 16 1999;130(4 Pt 1):322-4. [Medline]. [Full Text].

  94. Bastyr EJ 3rd, Stuart CA, Brodows RG, Schwartz S, Graf CJ, Zagar A, et al. Therapy focused on lowering postprandial glucose, not fasting glucose, may be superior for lowering HbA1c. IOEZ Study Group. Diabetes Care. Sep 2000;23(9):1236-41. [Medline]. [Full Text].

  95. Boyko EJ, Ahroni JH, Stensel V, Forsberg RC, Davignon DR, Smith DG. A prospective study of risk factors for diabetic foot ulcer. The Seattle Diabetic Foot Study. Diabetes Care. Jul 1999;22(7):1036-42. [Medline]. [Full Text].

  96. Branchi A, Rovellini A, Torri A, Sommariva D. Accuracy of calculated serum low-density lipoprotein cholesterol for the assessment of coronary heart disease risk in NIDDM patients. Diabetes Care. Sep 1998;21(9):1397-402. [Medline]. [Full Text].

  97. Brown JB, Nichols GA, Glauber HS, Bakst AW. Type 2 diabetes: incremental medical care costs during the first 8 years after diagnosis. Diabetes Care. Jul 1999;22(7):1116-24. [Medline]. [Full Text].

  98. Brown JB, Pedula KL, Bakst AW. The progressive cost of complications in type 2 diabetes mellitus. Arch Intern Med. Sep 13 1999;159(16):1873-80. [Medline].

  99. Buse JB, Henry RR, Han J, Kim DD, Fineman MS, Baron AD, et al. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in sulfonylurea-treated patients with type 2 diabetes. Diabetes Care. Nov 2004;27(11):2628-35. [Medline].

  100. Caixas A, Perez A, Qrdonez-Llanos J, Bonet R, Rigla M, Castellví A, et al. Lack of change of lipoprotein(a) levels by the optimization of glycemic control with insulin therapy in NIDDM patients. Diabetes Care. Sep 1997;20(9):1459-61. [Medline].

  101. [Best Evidence] Ceglia L, Lau J, Pittas AG. Meta-analysis: efficacy and safety of inhaled insulin therapy in adults with diabetes mellitus. Ann Intern Med. Nov 7 2006;145(9):665-75. [Medline].

  102. Chaiken RL, Khawaja R, Bard M, Eckert-Norton M, Banerji MA, Lebovitz HE. Utility of untimed urinary albumin measurements in assessing albuminuria in black NIDDM subjects. Diabetes Care. May 1997;20(5):709-13. [Medline].

  103. Chan JC, Chan KW, Ho LL, et al. An Asian multicenter clinical trial to assess the efficacy and tolerability of acarbose compared with placebo in type 2 diabetic patients previously treated with diet. Asian Acarbose Study Group. Diabetes Care. Jul 1998;21(7):1058-61. [Medline]. [Full Text].

  104. Chehade JM, Mooradian AD. A rational approach to drug therapy of type 2 diabetes mellitus. Drugs. Jul 2000;60(1):95-113. [Medline].

  105. Clark CM Jr. Combating sloth as well as gluttony: the role of physical fitness in mortality among men with type 2 diabetes. Ann Intern Med. Apr 18 2000;132(8):669-70. [Medline]. [Full Text].

  106. Cline GW, Petersen KF, Krssak M, Shen J, Hundal RS, Trajanoski Z, et al. Impaired glucose transport as a cause of decreased insulin-stimulated muscle glycogen synthesis in type 2 diabetes. N Engl J Med. Jul 22 1999;341(4):240-6. [Medline]. [Full Text].

  107. Colwell JA. Intensive insulin therapy in type II diabetes: rationale and collaborative clinical trial results. Diabetes. Jul 1996;45 Suppl 3:S87-90. [Medline].

  108. Colwell JA. The feasibility of intensive insulin management in non-insulin-dependent diabetes mellitus. Implications of the Veterans Affairs Cooperative Study on Glycemic Control and Complications in NIDDM. Ann Intern Med. Jan 1 1996;124(1 Pt 2):131-5. [Medline].

  109. Colwell JA, Nesto RW. The platelet in diabetes: focus on prevention of ischemic events. Diabetes Care. Jul 2003;26(7):2181-8. [Medline]. [Full Text].

  110. Coniff RF, Shapiro JA, Seaton TB. Long-term efficacy and safety of acarbose in the treatment of obese subjects with non-insulin-dependent diabetes mellitus. Arch Intern Med. Nov 14 1994;154(21):2442-8. [Medline].

  111. Damsbo P, Clauson P, Marbury TC, Windfeld K. A double-blind randomized comparison of meal-related glycemic control by repaglinide and glyburide in well-controlled type 2 diabetic patients. Diabetes Care. May 1999;22(5):789-94. [Medline]. [Full Text].

  112. Davis TM, Millns H, Stratton IM, Holman RR, Turner RC. Risk factors for stroke in type 2 diabetes mellitus: United Kingdom Prospective Diabetes Study (UKPDS) 29. Arch Intern Med. May 24 1999;159(10):1097-103. [Medline].

  113. Davis TM, Stratton IM, Fox CJ, Holman RR, Turner RC. U.K. Prospective Diabetes Study 22. Effect of age at diagnosis on diabetic tissue damage during the first 6 years of NIDDM. Diabetes Care. Sep 1997;20(9):1435-41. [Medline].

  114. de Lordes Lima M, Cruz T, Pousada JC, Rodrigues LE, Barbosa K, Canguçu V. The effect of magnesium supplementation in increasing doses on the control of type 2 diabetes. Diabetes Care. May 1998;21(5):682-6. [Medline]. [Full Text].

  115. DeFronzo RA. Pharmacologic therapy for type 2 diabetes mellitus. Ann Intern Med. Aug 17 1999;131(4):281-303. [Medline]. [Full Text].

  116. Diabetes Control and Complications Trial Research Group. The effect of intensive diabetes therapy on the development and progression of neuropathy. Ann Intern Med. Apr 15 1995;122(8):561-8. [Medline]. [Full Text].

  117. Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. Sep 30 1993;329(14):977-86. [Medline]. [Full Text].

  118. Dinneen SF, Gerstein HC. The association of microalbuminuria and mortality in non-insulin-dependent diabetes mellitus. A systematic overview of the literature. Arch Intern Med. Jul 14 1997;157(13):1413-8. [Medline].

  119. Eeley EA, Stratton IM, Hadden DR, et al. UKPDS 18: estimated dietary intake in type 2 diabetic patients randomly allocated to diet, sulphonylurea or insulin therapy. UK Prospective Diabetes Study Group. Diabet Med. Jul 1996;13(7):656-62. [Medline].

  120. Ehrmann DA, Barnes RB, Rosenfield RL, Cavaghan MK, Imperial J. Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome. Diabetes Care. Jan 1999;22(1):141-6. [Medline]. [Full Text].

  121. Emanuele N, Azad N, Abraira C, Henderson W, Colwell J, Levin S, et al. Effect of intensive glycemic control on fibrinogen, lipids, and lipoproteins: Veterans Affairs Cooperative Study in Type II Diabetes Mellitus. Arch Intern Med. Dec 7-21 1998;158(22):2485-90. [Medline].

  122. Enderle MD, Benda N, Schmuelling RM, Haering HU, Pfohl M. Preserved endothelial function in IDDM patients, but not in NIDDM patients, compared with healthy subjects. Diabetes Care. Feb 1998;21(2):271-7. [Medline].

  123. Engelgau MM, Narayan KM, Herman WH. Screening for type 2 diabetes. Diabetes Care. Oct 2000;23(10):1563-80. [Medline]. [Full Text].

  124. Estacio RO, Jeffers BW, Hiatt WR, Biggerstaff SL, Gifford N, Schrier RW. The effect of nisoldipine as compared with enalapril on cardiovascular outcomes in patients with non-insulin-dependent diabetes and hypertension. N Engl J Med. Mar 5 1998;338(10):645-52. [Medline]. [Full Text].

  125. Estacio RO, Regensteiner JG, Wolfel EE, Jeffers B, Dickenson M, Schrier RW. The association between diabetic complications and exercise capacity in NIDDM patients. Diabetes Care. Feb 1998;21(2):291-5. [Medline].

  126. Faas A, Schellevis FG, Van Eijk JT. The efficacy of self-monitoring of blood glucose in NIDDM subjects. A criteria-based literature review. Diabetes Care. Sep 1997;20(9):1482-6. [Medline].

  127. Fagan TC, Sowers J. Type 2 diabetes mellitus: greater cardiovascular risks and greater benefits of therapy. Arch Intern Med. May 24 1999;159(10):1033-4. [Medline].

  128. Fehse F, Trautmann M, Holst JJ, Halseth AE, Nanayakkara N, Nielsen LL. Exenatide augments first- and second-phase insulin secretion in response to intravenous glucose in subjects with type 2 diabetes. J Clin Endocrinol Metab. Nov 2005;90(11):5991-7. [Medline].

  129. Feinglos MN, Thacker CH, English J, Bethel MA, Lane JD. Modification of postprandial hyperglycemia with insulin lispro improves glucose control in patients with type 2 diabetes. Diabetes Care. Oct 1997;20(10):1539-42. [Medline].

  130. Ferris FL 3rd, Davis MD, Aiello LM. Treatment of diabetic retinopathy. N Engl J Med. Aug 26 1999;341(9):667-78. [Medline]. [Full Text].

  131. Forsblom CM, Groop PH, Ekstrand A, Tötterman KJ, Sane T, Saloranta C, et al. Predictors of progression from normoalbuminuria to microalbuminuria in NIDDM. Diabetes Care. Nov 1998;21(11):1932-8. [Medline]. [Full Text].

  132. Friedberg CE, Janssen MJ, Heine RJ, Grobbee DE. Fish oil and glycemic control in diabetes. A meta-analysis. Diabetes Care. Apr 1998;21(4):494-500. [Medline]. [Full Text].

  133. Frykberg RG, Lavery LA, Pham H, Harvey C, Harkless L, Veves A. Role of neuropathy and high foot pressures in diabetic foot ulceration. Diabetes Care. Oct 1998;21(10):1714-9. [Medline]. [Full Text].

  134. Gaster B, Hirsch IB. The effects of improved glycemic control on complications in type 2 diabetes. Arch Intern Med. Jan 26 1998;158(2):134-40. [Medline].

  135. Genuth S. Exogenous insulin administration and cardiovascular risk in non-insulin-dependent and insulin-dependent diabetes mellitus. Ann Intern Med. Jan 1 1996;124(1 Pt 2):104-9. [Medline].

  136. Golan L, Birkmeyer JD, Welch HG. The cost-effectiveness of treating all patients with type 2 diabetes with angiotensin-converting enzyme inhibitors. Ann Intern Med. Nov 2 1999;131(9):660-7. [Medline]. [Full Text].

  137. Goldberg RB. The benefits of lowering cholesterol in subjects with mild hyperglycemia. Arch Intern Med. Dec 13-27 1999;159(22):2627-8. [Medline].

  138. Goldberg RB, Einhorn D, Lucas CP, Rendell MS, Damsbo P, Huang WC, et al. A randomized placebo-controlled trial of repaglinide in the treatment of type 2 diabetes. Diabetes Care. Nov 1998;21(11):1897-903. [Medline]. [Full Text].

  139. Goldberg RB, Holvey SM, Schneider J. A dose-response study of glimepiride in patients with NIDDM who have previously received sulfonylurea agents. The Glimepiride Protocol #201 Study Group. Diabetes Care. Aug 1996;19(8):849-56. [Medline].

  140. Gray A, Raikou M, McGuire A, Fenn P, Stevens R, Cull C, et al. Cost effectiveness of an intensive blood glucose control policy in patients with type 2 diabetes: economic analysis alongside randomised controlled trial (UKPDS 41). United Kingdom Prospective Diabetes Study Group. BMJ. May 20 2000;320(7246):1373-8. [Medline]. [Full Text].

  141. Gress TW, Nieto FJ, Shahar E, Wofford MR, Brancati FL. Hypertension and antihypertensive therapy as risk factors for type 2 diabetes mellitus. Atherosclerosis Risk in Communities Study. N Engl J Med. Mar 30 2000;342(13):905-12. [Medline]. [Full Text].

  142. Grossman E, Messerli FH, Goldbourt U. High blood pressure and diabetes mellitus: are all antihypertensive drugs created equal?. Arch Intern Med. Sep 11 2000;160(16):2447-52. [Medline].

  143. Gumbiner B. Treating obesity in type 2 diabetes. Calories, composition, and control. Diabetes Care. Jun 1999;22(6):886-8. [Medline]. [Full Text].

  144. Gumbiner B, Low CC, Reaven PD. Effects of a monounsaturated fatty acid-enriched hypocaloric diet on cardiovascular risk factors in obese patients with type 2 diabetes. Diabetes Care. Jan 1998;21(1):9-15. [Medline].

  145. Haffner SM. Is there a glycemic threshold?. Arch Intern Med. Sep 8 1997;157(16):1791. [Medline].

  146. Haffner SM, Alexander CM, Cook TJ, Boccuzzi SJ, Musliner TA, Pedersen TR, et al. Reduced coronary events in simvastatin-treated patients with coronary heart disease and diabetes or impaired fasting glucose levels: subgroup analyses in the Scandinavian Simvastatin Survival Study. Arch Intern Med. Dec 13-27 1999;159(22):2661-7. [Medline].

  147. Haffner SM, Hanefeld M, Fischer S, Fuçker K, Leonhardt W. Glibenclamide, but not acarbose, increases leptin concentrations parallel to changes in insulin in subjects with NIDDM. Diabetes Care. Sep 1997;20(9):1430-4. [Medline].

  148. Haffner SM, Lehto S, Rönnemaa T, Pyörälä K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. Jul 23 1998;339(4):229-34. [Medline]. [Full Text].

  149. Harris EL, Sherman SH, Georgopoulos A. Black-white differences in risk of developing retinopathy among individuals with type 2 diabetes. Diabetes Care. May 1999;22(5):779-83. [Medline]. [Full Text].

  150. Harris MI, Eastman RC, Cowie CC, Flegal KM, Eberhardt MS. Racial and ethnic differences in glycemic control of adults with type 2 diabetes. Diabetes Care. Mar 1999;22(3):403-8. [Medline]. [Full Text].

  151. Harris MI, Klein R, Cowie CC, Rowland M, Byrd-Holt DD. Is the risk of diabetic retinopathy greater in non-Hispanic blacks and Mexican Americans than in non-Hispanic whites with type 2 diabetes? A U.S. population study. Diabetes Care. Aug 1998;21(8):1230-5. [Medline]. [Full Text].

  152. Heart Outcomes Prevention Evaluation Study Investigators. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Lancet. Jan 22 2000;355(9200):253-9. [Medline].

  153. Heilbronn LK, Noakes M, Clifton PM. Effect of energy restriction, weight loss, and diet composition on plasma lipids and glucose in patients with type 2 diabetes. Diabetes Care. Jun 1999;22(6):889-95. [Medline]. [Full Text].

  154. Hellman R, Regan J, Rosen H. Effect of intensive treatment of diabetes of the risk of death or renal failure in NIDDM and IDDM. Diabetes Care. Mar 1997;20(3):258-64. [Medline].

  155. Herman GA, Bergman A, Stevens C, Kotey P, Yi B, Zhao P. Effect of single oral doses of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on incretin and plasma glucose levels after an oral glucose tolerance test in patients with type 2 diabetes. J Clin Endocrinol Metab. Nov 2006;91(11):4612-9. [Medline].

  156. Heymsfield SB, Segal KR, Hauptman J, Lucas CP, Boldrin MN, Rissanen A, et al. Effects of weight loss with orlistat on glucose tolerance and progression to type 2 diabetes in obese adults. Arch Intern Med. May 8 2000;160(9):1321-6. [Medline].

  157. Hollander PA, Elbein SC, Hirsch IB, Kelley D, McGill J, Taylor T, et al. Role of orlistat in the treatment of obese patients with type 2 diabetes. A 1-year randomized double-blind study. Diabetes Care. Aug 1998;21(8):1288-94. [Medline]. [Full Text].

  158. Holman RR, Cull CA, Turner RC. A randomized double-blind trial of acarbose in type 2 diabetes shows improved glycemic control over 3 years (U.K. Prospective Diabetes Study 44). Diabetes Care. Jun 1999;22(6):960-4. [Medline]. [Full Text].

  159. Horton ES, Gavin JR, Kahn SE, Leahy JL, Conner CS, eds. Incretins and Type 2 Diabetes: The What, Why and How of New Therapeutic Options. Edgewood, CO: The Endocrine Society Continuing Medical Education Services; Nov 2006.

  160. Hypertension in Diabetes Study. HDS: I. Prevalence of hypertension in newly presenting type 2 diabetic patients and the association with risk factors for cardiovascular and diabetic complications. J Hypertens. Mar 1993;11(3):309-17. [Medline].

  161. Ilkova H, Glaser B, Tunçkale A, Bagriaçik N, Cerasi E. Induction of long-term glycemic control in newly diagnosed type 2 diabetic patients by transient intensive insulin treatment. Diabetes Care. Sep 1997;20(9):1353-6. [Medline].

  162. Ishii T, Yamakita T, Sato T, Tanaka S, Fujii S. Resistance training improves insulin sensitivity in NIDDM subjects without altering maximal oxygen uptake. Diabetes Care. Aug 1998;21(8):1353-5. [Medline]. [Full Text].

  163. Islam N, Kazmi F, Chusney GD, et al. Ethnic differences in correlates of microalbuminuria in NIDDM. The role of the acute-phase response. Diabetes Care. Mar 1998;21(3):385-8. [Medline]. [Full Text].

  164. Jacober SJ, Sowers JR. An update on perioperative management of diabetes. Arch Intern Med. Nov 8 1999;159(20):2405-11. [Medline].

  165. James SA, Jamjoum L, Raghunathan TE, Strogatz DS, Furth ED, Khazanie PG. Physical activity and NIDDM in African-Americans. The Pitt County Study. Diabetes Care. Apr 1998;21(4):555-62. [Medline]. [Full Text].

  166. Jick SS, Stender M, Myers MW. Frequency of liver disease in type 2 diabetic patients treated with oral antidiabetic agents. Diabetes Care. Dec 1999;22(12):2067-71. [Medline]. [Full Text].

  167. Johansen K. Efficacy of metformin in the treatment of NIDDM. Meta-analysis. Diabetes Care. Jan 1999;22(1):33-7. [Medline]. [Full Text].

  168. Johnson JL, Wolf SL, Kabadi UM. Efficacy of insulin and sulfonylurea combination therapy in type II diabetes. A meta-analysis of the randomized placebo-controlled trials. Arch Intern Med. Feb 12 1996;156(3):259-64. [Medline].

  169. Johnston PS, Feig PU, Coniff RF, Krol A, Davidson JA, Haffner SM. Long-term titrated-dose alpha-glucosidase inhibition in non-insulin-requiring Hispanic NIDDM patients. Diabetes Care. Mar 1998;21(3):409-15. [Medline]. [Full Text].

  170. Johnston PS, Feig PU, Coniff RF, Krol A, Kelley DE, Mooradian AD. Chronic treatment of African-American type 2 diabetic patients with alpha-glucosidase inhibition. Diabetes Care. Mar 1998;21(3):416-22. [Medline]. [Full Text].

  171. Järvi AE, Karlström BE, Granfeldt YE, Björck IE, Asp NG, Vessby BO. Improved glycemic control and lipid profile and normalized fibrinolytic activity on a low-glycemic index diet in type 2 diabetic patients. Diabetes Care. Jan 1999;22(1):10-8. [Medline]. [Full Text].

  172. Kang J, Robertson RJ, Hagberg JM, Kelley DE, Goss FL, DaSilva SG, et al. Effect of exercise intensity on glucose and insulin metabolism in obese individuals and obese NIDDM patients. Diabetes Care. Apr 1996;19(4):341-9. [Medline].

  173. Kanters SD, Algra A, Banga JD. Carotid intima-media thickness in hyperlipidemic type I and type II diabetic patients. Diabetes Care. Mar 1997;20(3):276-80. [Medline].

  174. Karter AJ, Rowell SE, Ackerson LM, Mitchell BD, Ferrara A, Selby JV, et al. Excess maternal transmission of type 2 diabetes. The Northern California Kaiser Permanente Diabetes Registry. Diabetes Care. Jun 1999;22(6):938-43. [Medline]. [Full Text].

  175. Kasiske BL, Kalil RS, Ma JZ, Liao M, Keane WF. Effect of antihypertensive therapy on the kidney in patients with diabetes: a meta-regression analysis. Ann Intern Med. Jan 15 1993;118(2):129-38. [Medline]. [Full Text].

  176. Kawagishi T, Nishizawa Y, Taniwaki H, Tanaka S, Okuno Y, Inaba M, et al. Relationship between gastric emptying and an alpha-glucosidase inhibitor effect on postprandial hyperglycemia in NIDDM patients. Diabetes Care. Oct 1997;20(10):1529-32. [Medline].

  177. Keilani T, Schlueter WA, Levin ML, Batlle DC. Improvement of lipid abnormalities associated with proteinuria using fosinopril, an angiotensin-converting enzyme inhibitor. Ann Intern Med. Feb 15 1993;118(4):246-54. [Medline]. [Full Text].

  178. Kelley DE, Bidot P, Freedman Z, Haag B, Podlecki D, Rendell M, et al. Efficacy and safety of acarbose in insulin-treated patients with type 2 diabetes. Diabetes Care. Dec 1998;21(12):2056-61. [Medline]. [Full Text].

  179. Kendall DM, Riddle MC, Rosenstock J, Zhuang D, Kim DD, Fineman MS. Effects of exenatide (exendin-4) on glycemic control over 30 weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea. Diabetes Care. May 2005;28(5):1083-91. [Medline].

  180. Klein R, Klein BE, Moss SE. Relation of glycemic control to diabetic microvascular complications in diabetes mellitus. Ann Intern Med. Jan 1 1996;124(1 Pt 2):90-6. [Medline].

  181. Klein R, Klein BE, Moss SE, Cruickshanks KJ. Relationship of hyperglycemia to the long-term incidence and progression of diabetic retinopathy. Arch Intern Med. Oct 10 1994;154(19):2169-78. [Medline].

  182. Kletter GG. Sliding scale fallacy. Arch Intern Med. Jul 13 1998;158(13):1472. [Medline].

  183. Kohner EM, Stratton IM, Aldington SJ, Turner RC, Matthews DR. Microaneurysms in the development of diabetic retinopathy (UKPDS 42). UK Prospective Diabetes Study Group. Diabetologia. Sep 1999;42(9):1107-12. [Medline].

  184. Koivisto VA, Tuominen JA, Ebeling P. Lispro Mix25 insulin as premeal therapy in type 2 diabetic patients. Diabetes Care. Mar 1999;22(3):459-62. [Medline]. [Full Text].

  185. Krolewski AS, Laffel LM, Krolewski M, et al. Glycosylated hemoglobin and the risk of microalbuminuria in patients with insulin-dependent diabetes mellitus. N Engl J Med. May 11 1995;332(19):1251-5. [Medline]. [Full Text].

  186. Lam KS, Tiu SC, Tsang MW, Ip TP, Tam SC. Acarbose in NIDDM patients with poor control on conventional oral agents. A 24-week placebo-controlled study. Diabetes Care. Jul 1998;21(7):1154-8. [Medline]. [Full Text].

  187. Larsen JJ, Dela F, Madsbad S, Vibe-Petersen J, Galbo H. Interaction of sulfonylureas and exercise on glucose homeostasis in type 2 diabetic patients. Diabetes Care. Oct 1999;22(10):1647-54. [Medline]. [Full Text].

  188. Lavery LA, Armstrong DG, Vela SA, Quebedeaux TL, Fleischli JG. Practical criteria for screening patients at high risk for diabetic foot ulceration. Arch Intern Med. Jan 26 1998;158(2):157-62. [Medline].

  189. Lehto S, Ronnemaa T, Pyorala K, Laakso M. Risk factors predicting lower extremity amputations in patients with NIDDM. Diabetes Care. Jun 1996;19(6):607-12. [Medline].

  190. Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl J Med. Nov 11 1993;329(20):1456-62. [Medline]. [Full Text].

  191. Lillioja S, Mott DM, Spraul M, Ferraro R, Foley JE, Ravussin E, et al. Insulin resistance and insulin secretory dysfunction as precursors of non-insulin-dependent diabetes mellitus. Prospective studies of Pima Indians. N Engl J Med. Dec 30 1993;329(27):1988-92. [Medline]. [Full Text].

  192. Lindsay RS, Hanson RL, Bennett PH, Knowler WC. Secular trends in birth weight, BMI, and diabetes in the offspring of diabetic mothers. Diabetes Care. Sep 2000;23(9):1249-54. [Medline]. [Full Text].

  193. Litzelman DK, Marriott DJ, Vinicor F. Independent physiological predictors of foot lesions in patients with NIDDM. Diabetes Care. Aug 1997;20(8):1273-8. [Medline].

  194. Lorber D. Nonketotic hypertonicity in diabetes mellitus. Med Clin North Am. Jan 1995;79(1):39-52. [Medline].

  195. Luo J, Rizkalla SW, Vidal H, Oppert JM, Colas C, Boussairi A, et al. Moderate intake of n-3 fatty acids for 2 months has no detrimental effect on glucose metabolism and could ameliorate the lipid profile in type 2 diabetic men. Results of a controlled study. Diabetes Care. May 1998;21(5):717-24. [Medline]. [Full Text].

  196. Maggio CA, Pi-Sunyer FX. The prevention and treatment of obesity. Application to type 2 diabetes. Diabetes Care. Nov 1997;20(11):1744-66. [Medline].

  197. Malerbi DA, Paiva ES, Duarte AL, Wajchenberg BL. Metabolic effects of dietary sucrose and fructose in type II diabetic subjects. Diabetes Care. Nov 1996;19(11):1249-56. [Medline].

  198. Malmberg K, Norhammar A, Wedel H, Ryden L. Glycometabolic state at admission: important risk marker of mortality in conventionally treated patients with diabetes mellitus and acute myocardial infarction: long-term results from the Diabetes and Insulin-Glucose Infusion in Acute MI. Circulation. May 25 1999;99(20):2626-32. [Medline]. [Full Text].

  199. Markovic TP, Campbell LV, Balasubramanian S, Jenkins AB, Fleury AC, Simons LA, et al. Beneficial effect on average lipid levels from energy restriction and fat loss in obese individuals with or without type 2 diabetes. Diabetes Care. May 1998;21(5):695-700. [Medline]. [Full Text].

  200. Markovic TP, Jenkins AB, Campbell LV, Furler SM, Kraegen EW, Chisholm DJ. The determinants of glycemic responses to diet restriction and weight loss in obesity and NIDDM. Diabetes Care. May 1998;21(5):687-94. [Medline]. [Full Text].

  201. Materson BJ. ACE inhibitors as a shield against diabetic nephropathy. Arch Intern Med. Feb 12 1996;156(3):239-40. [Medline].

  202. Matthews DR, Cull CA, Stratton IM, Holman RR, Turner RC. UKPDS 26: Sulphonylurea failure in non-insulin-dependent diabetic patients over six years. UK Prospective Diabetes Study (UKPDS) Group. Diabet Med. Apr 1998;15(4):297-303. [Medline].

  203. McCarron DA, Oparil S, Chait A, Haynes RB, Kris-Etherton P, Stern JS, et al. Nutritional management of cardiovascular risk factors. A randomized clinical trial. Arch Intern Med. Jan 27 1997;157(2):169-77. [Medline].

  204. McCormack J, Greenhalgh T. Seeing what you want to see in randomised controlled trials: versions and perversions of UKPDS data. United Kingdom prospective diabetes study. BMJ. Jun 24 2000;320(7251):1720-3. [Medline]. [Full Text].

  205. Meneilly GS, Elliott T. Metabolic alterations in middle-aged and elderly obese patients with type 2 diabetes. Diabetes Care. Jan 1999;22(1):112-8. [Medline]. [Full Text].

  206. Metz JA, Stern JS, Kris-Etherton P, Reusser ME, Morris CD, Hatton DC, et al. A randomized trial of improved weight loss with a prepared meal plan in overweight and obese patients: impact on cardiovascular risk reduction. Arch Intern Med. Jul 24 2000;160(14):2150-8. [Medline].

  207. Morris AD, McAlpine R, Steinke D, Boyle DI, Ebrahim AR, Vasudev N, et al. Diabetes and lower-limb amputations in the community. A retrospective cohort study. DARTS/MEMO Collaboration. Diabetes Audit and Research in Tayside Scotland/Medicines Monitoring Unit. Diabetes Care. May 1998;21(5):738-43. [Medline]. [Full Text].

  208. Moses R, Slobodniuk R, Boyages S, Colagiuri S, Kidson W, Carter J, et al. Effect of repaglinide addition to metformin monotherapy on glycemic control in patients with type 2 diabetes. Diabetes Care. Jan 1999;22(1):119-24. [Medline]. [Full Text].

  209. Moss SE, Klein R, Klein BE. Risk factors for hospitalization in people with diabetes. Arch Intern Med. Sep 27 1999;159(17):2053-7. [Medline].

  210. Moss SE, Klein R, Klein BE. The 14-year incidence of lower-extremity amputations in a diabetic population. The Wisconsin Epidemiologic Study of Diabetic Retinopathy. Diabetes Care. Jun 1999;22(6):951-9. [Medline]. [Full Text].

  211. Moss SE, Klein R, Klein BE, Meuer SM. The association of glycemia and cause-specific mortality in a diabetic population. Arch Intern Med. Nov 14 1994;154(21):2473-9. [Medline].

  212. Mäkimattila S, Liu ML, Vakkilainen J, Schlenzka A, Lahdenperä S, Syvänne M, et al. Impaired endothelium-dependent vasodilation in type 2 diabetes. Relation to LDL size, oxidized LDL, and antioxidants. Diabetes Care. Jun 1999;22(6):973-81. [Medline]. [Full Text].

  213. Nathan DM. Some answers, more controversy, from UKPDS. United Kingdom Prospective Diabetes Study. Lancet. Sep 12 1998;352(9131):832-3. [Medline].

  214. National Task Force on the Prevention and Treatment of Obesity. Overweight, obesity, and health risk. Arch Intern Med. Apr 10 2000;160(7):898-904. [Medline].

  215. Nelson RG, Bennett PH, Beck GJ, Tan M, Knowler WC, Mitch WE, et al. Development and progression of renal disease in Pima Indians with non-insulin-dependent diabetes mellitus. Diabetic Renal Disease Study Group. N Engl J Med. Nov 28 1996;335(22):1636-42. [Medline]. [Full Text].

  216. Nesto RW. Screening for asymptomatic coronary artery disease in diabetes. Diabetes Care. Sep 1999;22(9):1393-5. [Medline]. [Full Text].

  217. Nielsen FS, Sato A, Ali S, Tarnow L, Smidt UM, Kastrup J, et al. Beneficial impact of ramipril on left ventricular hypertrophy in normotensive nonalbuminuric NIDDM patients. Diabetes Care. May 1998;21(5):804-9. [Medline]. [Full Text].

  218. Nielsen S, Schmitz A, Poulsen PL, Hansen KW, Mogensen CE. Albuminuria and 24-h ambulatory blood pressure in normoalbuminuric and microalbuminuric NIDDM patients. A longitudinal study. Diabetes Care. Nov 1995;18(11):1434-41. [Medline].

  219. Niskanen L, Turpeinen A, Penttila I, Uusitupa MI. Hyperglycemia and compositional lipoprotein abnormalities as predictors of cardiovascular mortality in type 2 diabetes: a 15-year follow-up from the time of diagnosis. Diabetes Care. Nov 1998;21(11):1861-9. [Medline]. [Full Text].

  220. Osei K, Gaillard T, Schuster DP. Pathogenetic mechanisms of impaired glucose tolerance and type II diabetes in African-Americans. The significance of insulin secretion, insulin sensitivity, and glucose effectiveness. Diabetes Care. Mar 1997;20(3):396-404. [Medline].

  221. Pahor M, Psaty BM, Alderman MH, Applegate WB, Williamson JD, Furberg CD. Therapeutic benefits of ACE inhibitors and other antihypertensive drugs in patients with type 2 diabetes. Diabetes Care. Jul 2000;23(7):888-92. [Medline]. [Full Text].

  222. Pandit MK, Burke J, Gustafson AB, Minocha A, Peiris AN. Drug-induced disorders of glucose tolerance. Ann Intern Med. Apr 1 1993;118(7):529-39. [Medline]. [Full Text].

  223. Partanen J, Niskanen L, Lehtinen J, Mervaala E, Siitonen O, Uusitupa M. Natural history of peripheral neuropathy in patients with non-insulin-dependent diabetes mellitus. N Engl J Med. Jul 13 1995;333(2):89-94. [Medline]. [Full Text].

  224. Pedrini MT, Levey AS, Lau J, Chalmers TC, Wang PH. The effect of dietary protein restriction on the progression of diabetic and nondiabetic renal diseases: a meta-analysis. Ann Intern Med. Apr 1 1996;124(7):627-32. [Medline]. [Full Text].

  225. Peters AL, Hsueh W. Antihypertensive agents in diabetic patients: great benefits, special risks. Arch Intern Med. Mar 22 1999;159(6):541-2. [Medline].

  226. Peters AL, Legorreta AP, Ossorio RC. Quality of outpatient care provided to diabetic patients. A health maintenance organization experience. Diabetes Care. Jun 1996;19(6):601-6. [Medline].

  227. Pham H, Armstrong DG, Harvey C. Screening techniques to identify people at high risk for diabetic foot ulceration: a prospective multicenter trial. Diabetes Care. May 2000;23(5):606-11. [Medline].

  228. Pinhas-Hamiel O, Dolan LM, Zeitler PS. Diabetic ketoacidosis among obese African-American adolescents with NIDDM. Diabetes Care. Apr 1997;20(4):484-6. [Medline].

  229. Pittet D, Wyssa B, Herter-Clavel C. Outcome of diabetic foot infections treated conservatively: a retrospective cohort study with long-term follow-up. Arch Intern Med. Apr 26 1999;159(8):851-6. [Medline].

  230. Powers DR, Wallin JD. End-stage renal disease in specific ethnic and racial groups: risk factors and benefits of antihypertensive therapy. Arch Intern Med. Apr 13 1998;158(7):793-800. [Medline].

  231. Prando R, Cheli V, Melga P. Is type 2 diabetes a different disease in obese and nonobese patients?. Diabetes Care. Oct 1998;21(10):1680-5. [Medline].

  232. Prescribing information for sitagliptin (Januvia). Available at http://www.merck.com/product/usa/pi_circulars/j/januvia/januvia_pi.pdf. Accessed December 4, 2006.

  233. Ravid M, Brosh D, Levi Z. Use of enalapril to attenuate decline in renal function in normotensive, normoalbuminuric patients with type 2 diabetes mellitus. A randomized, controlled trial. Ann Intern Med. Jun 15 1998;128(12 Pt 1):982-8. [Medline].

  234. Ravid M, Brosh D, Ravid-Safran D. Main risk factors for nephropathy in type 2 diabetes mellitus are plasma cholesterol levels, mean blood pressure, and hyperglycemia. Arch Intern Med. May 11 1998;158(9):998-1004. [Medline].

  235. Ravid M, Lang R, Rachmani R. Long-term renoprotective effect of angiotensin-converting enzyme inhibition in non-insulin-dependent diabetes mellitus. A 7-year follow-up study. Arch Intern Med. Feb 12 1996;156(3):286-9. [Medline].

  236. Ravid M, Savin H, Jutrin I. Long-term stabilizing effect of angiotensin-converting enzyme inhibition on plasma creatinine and on proteinuria in normotensive type II diabetic patients. Ann Intern Med. Apr 15 1993;118(8):577-81. [Medline].

  237. Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes. Dec 1988;37(12):1595-607. [Medline].

  238. Reaven GM. Intensive blood pressure/glucose control in type 2 diabetes: why is it so difficult to decrease coronary heart disease?. J Hum Hypertens. Apr 1999;13 Suppl 2:S19-23; discussion S25-8. [Medline].

  239. Reaven GM. Resistance to insulin-stimulated glucose uptake and hyperinsulinemia: role in non-insulin-dependent diabetes, high blood pressure, dyslipidemia and coronary heart disease. Diabete Metab. May 1991;17(1 Pt 2):78-86. [Medline].

  240. Reaven GM. Role of insulin resistance in human disease (syndrome X): an expanded definition. Annu Rev Med. 1993;44:121-31. [Medline].

  241. Reaven GM. Role of insulin resistance in the pathophysiology of non-insulin dependent diabetes mellitus. Diabetes Metab Rev. Nov 1993;9 Suppl 1:5S-12S. [Medline].

  242. Reaven GM. The role of insulin resistance and hyperinsulinemia in coronary heart disease. Metabolism. May 1992;41(5 Suppl 1):16-9. [Medline].

  243. Redmon JB, Raatz SK, Kwong CA. Pharmacologic induction of weight loss to treat type 2 diabetes. Diabetes Care. Jun 1999;22(6):896-903. [Medline].

  244. Reiber GE, Pecoraro RE, Koepsell TD. Risk factors for amputation in patients with diabetes mellitus. A case-control study. Ann Intern Med. Jul 15 1992;117(2):97-105. [Medline].

  245. Resnick HE, Valsania P, Phillips CL. Diabetes mellitus and nontraumatic lower extremity amputation in black and white Americans: the National Health and Nutrition Examination Survey Epidemiologic Follow-up Study, 1971-1992. Arch Intern Med. Nov 8 1999;159(20):2470-5. [Medline].

  246. Rich-Edwards JW, Colditz GA, Stampfer MJ. Birthweight and the risk for type 2 diabetes mellitus in adult women. Ann Intern Med. Feb 16 1999;130(4 Pt 1):278-84. [Medline].

  247. Riddle MC, Drucker DJ. Emerging therapies mimicking the effects of amylin and glucagon-like peptide 1. Diabetes Care. Feb 2006;29(2):435-49. [Medline].

  248. Riddle MC, McDaniel PA, Tive LA. Glipizide-GITS does not increase the hypoglycemic effect of mild exercise during fasting in NIDDM. Diabetes Care. Jun 1997;20(6):992-4. [Medline].

  249. Riddle MC, Schneider J. Beginning insulin treatment of obese patients with evening 70/30 insulin plus glimepiride versus insulin alone. Glimepiride Combination Group. Diabetes Care. Jul 1998;21(7):1052-7. [Medline].

  250. Ritz E, Orth SR. Nephropathy in patients with type 2 diabetes mellitus. N Engl J Med. Oct 7 1999;341(15):1127-33. [Medline].

  251. Rivellese AA, Maffettone A, Iovine C. Long-term effects of fish oil on insulin resistance and plasma lipoproteins in NIDDM patients with hypertriglyceridemia. Diabetes Care. Nov 1996;19(11):1207-13. [Medline].

  252. Rosenbloom AL, Joe JR, Young RS. Emerging epidemic of type 2 diabetes in youth. Diabetes Care. Feb 1999;22(2):345-54. [Medline].

  253. Rosenstock J, Brown A, Fischer J. Efficacy and safety of acarbose in metformin-treated patients with type 2 diabetes. Diabetes Care. Dec 1998;21(12):2050-5. [Medline].

  254. Rosenstock J, Samols E, Muchmore DB. Glimepiride, a new once-daily sulfonylurea. A double-blind placebo-controlled study of NIDDM patients. Glimepiride Study Group. Diabetes Care. Nov 1996;19(11):1194-9. [Medline].

  255. Sattar N, Jaap AJ. Hormone replacement preparations and hypertriglyceridemia in women with NIDDM. Diabetes Care. Feb 1997;20(2):234-5. [Medline].

  256. Savage PJ, Pressel SL, Curb JD. Influence of long-term, low-dose, diuretic-based, antihypertensive therapy on glucose, lipid, uric acid, and potassium levels in older men and women with isolated systolic hypertension: Systolic Hypertension in the Elderly Program (SHEP) Cooperative. Arch Intern Med. Apr 13 1998;158(7):741-51. [Medline].

  257. Savage S, Estacio RO, Jeffers B. Urinary albumin excretion as a predictor of diabetic retinopathy, neuropathy, and cardiovascular disease in NIDDM. Diabetes Care. Nov 1996;19(11):1243-8. [Medline].

  258. Segal P, Feig PU, Schernthaner G. The efficacy and safety of miglitol therapy compared with glibenclamide in patients with NIDDM inadequately controlled by diet alone. Diabetes Care. May 1997;20(5):687-91. [Medline].

  259. Shah M, Garg A. High-fat and high-carbohydrate diets and energy balance. Diabetes Care. Oct 1996;19(10):1142-52. [Medline].

  260. Shepherd PR, Kahn BB. Glucose transporters and insulin action--implications for insulin resistance and diabetes mellitus. N Engl J Med. Jul 22 1999;341(4):248-57. [Medline].

  261. Shorr RI, Ray WA, Daugherty JR. Incidence and risk factors for serious hypoglycemia in older persons using insulin or sulfonylureas. Arch Intern Med. Aug 11-25 1997;157(15):1681-6. [Medline].

  262. Smulders YM, Rakic M, Stehouwer CD. Determinants of progression of microalbuminuria in patients with NIDDM.A prospective study. Diabetes Care. Jun 1997;20(6):999-1005. [Medline].

  263. Sowers JR. Diabetes mellitus and cardiovascular disease in women. Arch Intern Med. Mar 23 1998;158(6):617-21. [Medline].

  264. Stratton IM, Adler AI, Neil HA. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. Aug 12 2000;321(7258):405-12. [Medline].

  265. Sundaresan P, Lykos D, Daher A. Comparative effects of glibenclamide and metformin on ambulatory blood pressure and cardiovascular reactivity in NIDDM. Diabetes Care. May 1997;20(5):692-7. [Medline].

  266. Sundaresan P, Lykos D, Daher A. Comparative effects of glibenclamide and metformin on ambulatory blood pressure and cardiovascular reactivity in NIDDM. Diabetes Care. May 1997;20(5):692-7. [Medline].

  267. Tatti P, Pahor M, Byington RP. Outcome results of the Fosinopril Versus Amlodipine Cardiovascular Events Randomized Trial (FACET) in patients with hypertension and NIDDM. Diabetes Care. Apr 1998;21(4):597-603. [Medline].

  268. Thaler LM, El-Kebbi IM, Ziemer DC. High prevalence of albuminuria among African-Americans with short duration of diabetes. Diabetes Care. Sep 1998;21(9):1576-7. [Medline].

  269. Thompson D, Edelsberg J, Colditz GA. Lifetime health and economic consequences of obesity. Arch Intern Med. Oct 11 1999;159(18):2177-83. [Medline].

  270. Tikkanen MJ, Laakso M, Ilmonen M. Treatment of hypercholesterolemia and combined hyperlipidemia with simvastatin and gemfibrozil in patients with NIDDM. A multicenter comparison study. Diabetes Care. Apr 1998;21(4):477-81. [Medline].

  271. Tonolo G, Ciccarese M, Brizzi P. Reduction of albumin excretion rate in normotensive microalbuminuric type 2 diabetic patients during long-term simvastatin treatment. Diabetes Care. Dec 1997;20(12):1891-5. [Medline].

  272. Turner R, Cull C, Holman R. United Kingdom Prospective Diabetes Study 17: a 9-year update of a randomized, controlled trial on the effect of improved metabolic control on complications in non-insulin-dependent diabetes mellitus. Ann Intern Med. Jan 1 1996;124(1 Pt 2):136-45. [Medline].

  273. Turner R, Holman R, Butterfield J. UKPDS: what was the question? UK Prospective Diabetes Study. Lancet. Aug 14 1999;354(9178):600. [Medline].

  274. Turner R, Stratton I, Horton V. UKPDS 25: autoantibodies to islet-cell cytoplasm and glutamic acid decarboxylase for prediction of insulin requirement in type 2 diabetes. UK Prospective Diabetes Study Group [published erratum appears in Lancet 1998 Jan 31;351(9099):376]. Lancet. Nov 1 1997;350(9087):1288-93. [Medline].

  275. Turner RC. The U.K. Prospective Diabetes Study. A review. Diabetes Care. Dec 1998;21 Suppl 3:C35-8. [Medline].

  276. UK Prospective Diabetes Study Group. Cost effectiveness analysis of improved blood pressure control in hypertensive patients with type 2 diabetes: UKPDS 40. BMJ. Sep 12 1998;317(7160):720-6. [Medline].

  277. UK Prospective Diabetes Study. UKPDS 13: Relative efficacy of randomly allocated diet, sulphonylurea, insulin, or metformin in patients with newly diagnosed non-insulin dependent diabetes followed for three years. BMJ. Jan 14 1995;310(6972):83-8. [Medline].

  278. UK Prospective Diabetes Study. UKPDS 27. Plasma lipids and lipoproteins at diagnosis of NIDDM by age and sex. Diabetes Care. Nov 1997;20(11):1683-7. [Medline].

  279. UK Prospective Diabetes Study. UKPDS 7: response of fasting plasma glucose to diet therapy in newly presenting type II diabetic patients, UKPDS Group. Metabolism. Sep 1990;39(9):905-12. [Medline].

  280. UK Prospective Diabetes Study. UKPDS IX: Relationships of urinary albumin and N-acetylglucosaminidase to glycaemia and hypertension at diagnosis of type 2 (non-insulin-dependent) diabetes mellitus and after 3 months diet therapy. Diabetologia. Sep 1993;36(9):835-42. [Medline].

  281. UK Prospective Diabetes Study. UKPDS VIII. Study design, progress and performance. Diabetologia. Dec 1991;34(12):877-90. [Medline].

  282. UK Prospective Diabetes Study. UKPDS X. Urinary albumin excretion over 3 years in diet-treated type 2, (non-insulin-dependent) diabetic patients, and association with hypertension, hyperglycaemia and hypertriglyceridaemia. Diabetologia. Oct 1993;36(10):1021-9. [Medline].

  283. UK Prospective Diabetes Study. United Kingdom Prospective Diabetes Study 24: a 6-year, randomized, controlled trial comparing sulfonylurea, insulin, and metformin therapy in patients with newly diagnosed type 2 diabetes that could not be controlled with diet therapy. United Kingdom. Ann Intern Med. Feb 1 1998;128(3):165-75. [Medline].

  284. UK Prospective Diabetes Study Group. Quality of life in type 2 diabetic patients is affected by complications but not by intensive policies to improve blood glucose or blood pressure control (UKPDS 37). Diabetes Care. Jul 1999;22(7):1125-36. [Medline].

  285. Valmadrid CT, Klein R, Moss SE. The risk of cardiovascular disease mortality associated with microalbuminuria and gross proteinuria in persons with older-onset diabetes mellitus. Arch Intern Med. Apr 24 2000;160(8):1093-100. [Medline].

  286. Vanzetto G, Halimi S, Hammoud T. Prediction of cardiovascular events in clinically selected high-risk NIDDM patients. Prognostic value of exercise stress test and thallium-201 single-photon emission computed tomography. Diabetes Care. Jan 1999;22(1):19-26. [Medline].

  287. Vuksan V, Sievenpiper JL, Koo VY. American ginseng (Panax quinquefolius L) reduces postprandial glycemia in nondiabetic subjects and subjects with type 2 diabetes mellitus. Arch Intern Med. Apr 10 2000;160(7):1009-13. [Medline].

  288. Wagenknecht LE, D'Agostino RB Jr, Haffner SM. Impaired glucose tolerance, type 2 diabetes, and carotid wall thickness: the Insulin Resistance Atherosclerosis Study. Diabetes Care. Nov 1998;21(11):1812-8. [Medline].

  289. Wagner AM, Perez A, Calvo F. Apolipoprotein(B) identifies dyslipidemic phenotypes associated with cardiovascular risk in normocholesterolemic type 2 diabetic patients. Diabetes Care. May 1999;22(5):812-7. [Medline].

  290. Walker KZ, Piers LS, Putt RS. Effects of regular walking on cardiovascular risk factors and body composition in normoglycemic women and women with type 2 diabetes. Diabetes Care. Apr 1999;22(4):555-61. [Medline].

  291. Wang SL, Head J, Stevens L. Excess mortality and its relation to hypertension and proteinuria in diabetic patients. The world health organization multinational study of vascular disease in diabetes. Diabetes Care. Apr 1996;19(4):305-12. [Medline].

  292. Wannamethee SG, Shaper AG. Weight change and duration of overweight and obesity in the incidence of type 2 diabetes. Diabetes Care. Aug 1999;22(8):1266-72. [Medline].

  293. Wannamethee SG, Shaper AG, Alberti KG. Physical activity, metabolic factors, and the incidence of coronary heart disease and type 2 diabetes. Arch Intern Med. Jul 24 2000;160(14):2108-16. [Medline].

  294. Wannamethee SG, Shaper AG, Walker M. Lifestyle and 15-year survival free of heart attack, stroke, and diabetes in middle-aged British men. Arch Intern Med. Dec 7-21 1998;158(22):2433-40. [Medline].

  295. Warram JH, Manson JE, Krolewski AS. Glycosylated hemoglobin and the risk of retinopathy in insulin-dependent diabetes mellitus. N Engl J Med. May 11 1995;332(19):1305-6. [Medline].

  296. Wei M, Gaskill SP, Haffner SM. Effects of diabetes and level of glycemia on all-cause and cardiovascular mortality. The San Antonio Heart Study. Diabetes Care. Jul 1998;21(7):1167-72. [Medline].

  297. Wei M, Gibbons LW, Kampert JB. Low cardiorespiratory fitness and physical inactivity as predictors of mortality in men with type 2 diabetes. Ann Intern Med. Apr 18 2000;132(8):605-11. [Medline].

  298. Wei M, Gibbons LW, Mitchell TL. The association between cardiorespiratory fitness and impaired fasting glucose and type 2 diabetes mellitus in men [published erratum appears in Ann Intern Med 1999 Sep 7;131(5):394]. Ann Intern Med. Jan 19 1999;130(2):89-96. [Medline].

  299. Wieman TJ, Smiell JM, Su Y. Efficacy and safety of a topical gel formulation of recombinant human platelet-derived growth factor-BB (becaplermin) in patients with chronic neuropathic diabetic ulcers. A phase III randomized placebo-controlled double-blind study. Diabetes Care. May 1998;21(5):822-7. [Medline].

  300. Willey KA, Kidd JF, Harris JP. Albuminuria is an independent predictor of carotid intima-media thickness and atherosclerosis in NIDDM patients. Diabetes Care. Nov 1995;18(11):1502-3. [Medline].

  301. Williams KV, Mullen ML, Kelley DE. The effect of short periods of caloric restriction on weight loss and glycemic control in type 2 diabetes. Diabetes Care. Jan 1998;21(1):2-8. [Medline].

  302. Wolffenbuttel BH, Landgraf R. A 1-year multicenter randomized double-blind comparison of repaglinide and glyburide for the treatment of type 2 diabetes. Dutch and German Repaglinide Study Group. Diabetes Care. Mar 1999;22(3):463-7. [Medline].

  303. Wolffenbuttel BH, Sels JP, Rondas-Colbers GJ. Comparison of different insulin regimens in elderly patients with NIDDM. Diabetes Care. Dec 1996;19(12):1326-32. [Medline].

  304. Wollesen F, Dahlen G, Berglund L. Peripheral atherosclerosis and serum lipoprotein(a) in diabetes. Diabetes Care. Jan 1999;22(1):93-8. [Medline].

  305. Yamamoto M, Egusa G, Yamakido M. Carotid atherosclerosis and serum lipoprotein(a) concentrations in patients with NIDDM. Diabetes Care. May 1997;20(5):829-31. [Medline].

  306. Yki-Jarvinen H, Ryysy L, Nikkila K. Comparison of bedtime insulin regimens in patients with type 2 diabetes mellitus. A randomized, controlled trial. Ann Intern Med. Mar 2 1999;130(5):389-96. [Medline].

  307. Yusuf S, Sleight P, Pogue J. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators. N Engl J Med. Jan 20 2000;342(3):145-53. [Medline].

[ CLOSE WINDOW ]

Further Reading

Clinical guidelines:
American Association of Clinical Endocrinologists medical guidelines for clinical practice for the management of diabetes mellitus. Diabetes management in the hospital setting. American Association of Clinical Endocrinologists - Medical Specialty Society
American College of Endocrinology - Medical Specialty Society. 2000 Jan (revised 2007). 5 pages. NGC:005859

American Association of Clinical Endocrinologists medical guidelines for clinical practice for the management of diabetes mellitus. Nutrition and diabetes. American Association of Clinical Endocrinologists - Medical Specialty Society
American College of Endocrinology - Medical Specialty Society. 2000 Jan (revised 2007). 4 pages. NGC:005856

American Association of Clinical Endocrinologists medical guidelines for clinical practice for the management of diabetes mellitus. Prevention of type 2 diabetes mellitus. American Association of Clinical Endocrinologists - Medical Specialty Society
American College of Endocrinology - Medical Specialty Society. 2000 Jan (revised 2007). 4 pages. NGC:005852

Diagnosis and management of type 2 diabetes mellitus in adults. Institute for Clinical Systems Improvement - Private Nonprofit Organization. 1996 Mar (revised 2008 Mar). 89 pages. NGC:006581

Nutrition recommendations and interventions for diabetes: a position statement of the American Diabetes Association. American Diabetes Association - Professional Association. 1998 (revised 2008 Jan). 18 pages. NGC:006285

Clinical trials:
A Study to Evaluate the Postprandial Metabolic Response After Use of Glucerna SR in Obese Type 2 Diabetes

Effect of GlucoNorm vs Glyburide on Post-Prandial Hyperglycemia in Elderly Subjects With Type 2 Diabetes

Gene Expression Profiling and Bioinformatic Analysis Identifying Genes and Biochemical Pathways in Type 2 Diabetes

Health Benefits of Aerobic and Resistance Training in Individuals With Type 2 Diabetes (HART-D)

Vitamin D for the Prevention of Diabetes Type 2

[ CLOSE WINDOW ]

Keywords

diabetes mellitus, diabetes, insulin, glucose, blood sugar, metformin, diabetes type 2, diabetic, diabetes 2, hyperglycemia, diabetes diet, diabetes treatment, mellitus, diabetes mellitus type 2, diabetic ketoacidosis, diabetes symptoms, ketoacidosis, diabetes diagnosis, high blood sugar, type 2 diabetes mellitus, type II diabetes mellitus, DM, DM type 2, adult-onset diabetes mellitus, maturity-onset diabetes mellitus, non–insulin-dependent diabetes mellitus, NIDDM, maturity-onset diabetes of the young, MODY, microvascular complications, macrovascular complications, lack of endogenous insulin, pancreatic beta-cellfailure, insulinresistance,elevated free fatty acids, obesity, metabolic complications, insulin deficiency, end-stage renal disease, ESRD, nontraumatic lower limb amputations, diabetic vasculopathy, diabetic neuropathy, diabetic retinopathy, diabetic nephropathy, polyuria, polydipsia, polyphagia, blurred vision, lower extremity paresthesias, yeast infections, hypertension, high triglycerides,polycystic ovary disease, Cushing syndrome, acromegaly, pheochromocytoma, incretins, dipeptidyl-peptidase inhibitor-IV, DPP-4 inhibitor, gestational diabetes mellitus

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Kenneth Patrick L Ligaray, MD, Fellow, Department of Endocrinology, Diabetes and Metabolism, St Louis University
Kenneth Patrick L Ligaray, MD is a member of the following medical societies: American Association of Clinical Endocrinologists and Endocrine Society
Disclosure: Nothing to disclose.

Coauthor(s)

William L Isley, MD, Senior Associate Consultant, Associate Professor of Medicine, Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic of Rochester
William L Isley, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians, American Diabetes Association, American Federation for Medical Research, Endocrine Society, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Medical Editor

David S Schade, MD, Chief, Division of Endocrinology and Metabolism, Professor, Department of Internal Medicine, University of New Mexico School of Medicine and Health Sciences Center
David S Schade, MD is a member of the following medical societies: American College of Physicians, American Diabetes Association, American Federation for Medical Research, Endocrine Society, New Mexico Medical Society, New York Academy of Sciences, and Society for Experimental Biology and Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Don S Schalch, MD, Professor Emeritus, Department of Internal Medicine, Division of Endocrinology, University of Wisconsin Hospitals and Clinics
Don S Schalch, MD is a member of the following medical societies: American Diabetes Association, American Federation for Medical Research, Central Society for Clinical Research, and Endocrine Society
Disclosure: Nothing to disclose.

CME Editor

Mark Cooper, MBBS, PhD, FRACP, Head, Diabetes & Metabolism Division, Baker Heart Research Institute, Professor of Medicine, Monash University
Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD, Professor of Medicine, St Louis University School of Medicine
George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Medical Practice Executives, American College of Physician Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical Research, Endocrine Society, International Society for Clinical Densitometry, and Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

All material on this website is protected by copyright, Copyright© 1994- by Medscape.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.