Diabetes Mellitus Type 2

From Anvita Health Wiki

Contents 1 More Specific Terms 2 Etiology 3 Epidemiology 4 Pathology 5 Genetics 6 Clinical-manifestations 7 Laboratory 8 Diagnostic-procedures 9 Complications 10 Management 11 More General Terms 12 Additional Terms 13 Internet Database 14 References

More Specific Terms

• insulin-resistant diabetes mellitus with acanthosis nigricans
• leprechaunism (Donohue syndrome)
• mature onset diabetes of the young (MODY)
• Rabson-Mendenhall syndrome (Mendenhall syndrome)

Etiology

• insulin resistance

• decreased numbers of insulin receptors
• post-receptor mechanism

• impaired beta-cell function

• loss of 1st phase of insulin secretion

• mutations (rare)

• insulin
• insulin receptor
• glucokinase

• risk factors (see risk factors for diabetes mellitus type 2)

• age > 45 years
• obese individuals
• western culture diet
• lack of exercise
• previous gestational diabetes
• impaired glucose tolerance
• higher fasting plasma glucose within the normal range is a risk factor for young men [25]
• black, hispanic or native American ethnicity
• habitual sleep duration of < 6 hours/night
• hypertension - use of diuretics & beta blockers [29]
• coffee ?, see coffee & risk of diabetes
• smoking (see CARDIA study)
• increased weight gain relative to height during an infant's first 3 months of life [49]

Epidemiology

• common in developed nations

Pathology

• disease often present for 5-10 years prior to diagnosis

• retinopathy, neuropathy & nephropathy are commonly seen at clinical presentation

• non-enzymatic glycosylation of proteins (formation of AGE pigments)
• abnormalities in neutrophil function [3]

• defective chemotaxis
• impairment of neutrophil phagocytosis

• endothelial dysfunction associated with insulin-resistance
• insulin resistance correlates with & may be caused by RBP4
• effects of glucagon-like peptide may be attenuated
• glucagon NOT supressed in post-prandial state

Genetics

• stronger genetic susceptibility than type 1 diabetes
• 25% probability of having affected parent or sibling
• may be associated with mutation in the peroxisome proliferator receptor-gamma ( PPAR-gamma)
• associated wih defects in MAPK8IP1
• susceptibility to diabetes mellitus type 2: PPP1R3A, MCF2L2, TCF7L2
• susceptbility to microvascular complications:

• polymorphism(s) in EPO

• other implicated genes SLC30A8, INPPL1, CAPN10, MT-ND1, SLC22A2, AKT2, TGM2, HNF1B, ADRB3, INSR, GCGR, ABCC8, GLUT4, UCP1, BTC, KCNJ11, PDX1

Clinical-manifestations

• symptoms insidious in onset
• polyuria
• polydipsia, polyphagia
• fatigue
• chronic cutaneous infections
• yeast vaginitis
• blurred vision
• diabetic retinopathy:

• often present at the time of diagnosis
• retinal microaneurysms
• dot-blot hemorrhages
• macular edema

• peripheral neuropathy

• classic stocking-glove pattern

• paresthesias, especially of feet

• cranial nerve III palsy

• most patients are obese (> 120% of ideal body weight)

Laboratory

• fasting plasma glucose > 126 mg/dL on 2 separate occasions
• glucose tolerance test if glucose 120-140 mg/dL
• urinalysis

• glycosuria: occurs when serum glucose exceeds renal threshold, about 175 mg/dL; renal threshold may be as high as 250-300 mg/dL in diabetics
• proteinuria: albumin normally 10% of urine protein normal: < 100 mg or protein excreted in urine per day
• albumin/creatinine ratio annually

• glycated hemoglobin

• hemoglobin A1c

• target: < 7.0%
• high risk: > 8.5%

• total glycated hemoglobin
• measure every 2-3 months

• C-peptide in serum is measurable
• serology: (not routine) ICA1 autoantibody

Diagnostic-procedures

• routine myocardial perfusion screening of no benefit [47]

Complications

• increase in fatal myocardial infarction ( MI) in diabetics

• two-fold increase in diabetic men
• three-fold increase in diabetic women
• manifestations of angina & MI are often atypical
• incidence of silent myocardial infarction is high

• increased incidence of peripheral vascular disease & ischemic stroke
• hyperlipidemia
• diabetic nephropathy
• diabetic retinopathy
• diabetic polyneuropathy - diabetic foot
• 3-fold increase in mortality from pneumonia & influenza [25]
• gastroparesis

• gastric emptying generally accelerated in diabetes

• may be increased incidence of dementia

• contributions from ischemia & hypoglycemia [46]

• may increase risk of acute pancreatitis [64]
• at any given T-score or FRAX score, risk of fracture is increased relative to non-diabetic patients [68]
  
• disease interaction(s) of diabetes mellitus with urinary incontinence

Management

• diet

• most important management strategy in type 2 diabetes
• calorie restriction
• for many patients, diet control is more optimism than science [19]
• Mediterranean diet improves glycemic control in new onset type-2 diabetes [52]

• regular exercise

• combination of aerobic exercise & resistance training better than either alone [62]
• exercise capacity is associated with increased survival [63]
• exercise may be less important than diet [69]
• precautions

• check fasting glucose prior to vigorous exercise
• rapidly absorbed carbohydrate prior to extended exercise if glucose is low
• avoid exercise within 4 h of regular insulin
• avoid jogging/ running if neuropathy or peripheral vascular disease is present
• avoid resistance training if retinopathy is present due to risk of ocular hemorrhage

• goals of glycemic control

• glycemic targets & glucose-lowering treatments should be tailored to the individual patient [78]
• goal of hemoglobin A1c <= 7.0% not evidence-based [51]

• may not diminish risk of retinopathy & nephropathy, neuropathy [43]
• may not diminish risk of cardiovascular disease [43]
• goal of hemoglobin A1c <= 6.5% may increase mortality
• see ACCORD trial, ADVANCE trial, UKPD study, VADT trial
• tight glycemic control may do more harm than benefit; increases risk of severe hypoglycemia [51]
• intensive glucose control reduces non-fatal myocardial infarction, but not 5-year mortality [53]
• tight glycemic control may diminish cardiovascular events in diabetics with few comorbidities, but not those with substantial comorbidities [54,55]
• U-shaped mortality curve with respect to hemoglobin A1c; HbA1c of 6.4% & HbA1c of 10.6% with significantly higher mortality rates than HbA1c of 7.5% [56]

• goal of preprandial glucose 70-130 mg/dL [3]

• may increase risk of severe hypoglycemia [51,56]

• goal of 1-2 hour postprandial glucose < 180 mg/dL [3]

• pharmaceutical agents - hypoglycemic agents

• indications:

• when diet, exercise, & weight loss fail to improve hyperglycemia [73]

• use oral combination therapy early

• do not push monotherapy to maximum dose before adding a second agent [3]
• no combination therapy is recommended over another [73]

• metformin ( Glucophage)

• start 500 mg PO BID or 850 mg PO TID
• optimal dose: 1000 mg BID
• initial drug of choice [22,33,73,78]
• may be used in combination with orlistat
• useful for overweight patients [8]
• do not use if serum creatinine >= 1.5 mg/dL
• 10% lower risk of cancer relative to sulfonylurea [74]

• thiazoladinediones ( glitazones)

• may be used as 1st line agents [22,33]
• may diminish progression of atherosclerosis relative to sulfonylureas [34]
• avoid in patients with heart failure, CAD

• glitazars introduced in 2005
• sulfonylureas should be relegated to 3rd line agents [26]

• glipizide (Glucatrol) preferred agent in the elderly

• insulin

• insulin for symptomatic patients, converting later to oral hypoglycemic (if feasible)
• evening dose of NPH or glargine added to oral hypoglycemic agent(s) [13]

• start 10 units QHS
• target morning glucose < 150 mg/dL 80-120 mg/dL [3])
• glargine may be associated with less hypoglycemia than NPH
• continuing metformin in patients who require insulin is associated with better glycemic control, but not all-cause or cardiovascular mortality [79]

• addition of glargine or rosiglitazone to combination therapy of metformin plus sulfonylurea of similar initial efficacy [28]

• acarbose ( Precose)

• inhibits alpha glucosidase
• used in conjunction with sulfonylurea

• repaglinide & nateglinide
• exenatide ( Byetta) may also promote weight reduction [30]

• may be use in combination with metformin, sulfonylurea or insulin [66]

• pramilintide
• gliptins: sitagliptin, saxagliptin, vildagliptin
• rimonabant ( Acomplia) may be of benefit
• bromocriptine ( Cycloset) FDA-approved 2009 [57]
• cinnamon probably of no benefit [18]
• for type-2 diabetes not controlled by metformin + a sulfonylurea, no add-on drug has an obvious advantage over another [67]

• control of risk factors & concurrent disorders

• dyslipidemia

• goals:

• LDL cholesterol < 100 mg/dL
• HDL cholesterol > 40 mg/dL (men); > 50 mg/dL (women)
• serum triglycerides < 150 mg/dL is unfounded - no benefit of fibrate (see ACCORD trial, Field study)

• HMG CoA reductase inhibitor (statin) even if cholesterol levels are at target [12,17,20,31]
• see use of HMG CoA reductase inhibitors ( statins) ...

• cardiovascular disease

• control of dyslipidemia (see above)
• diet & exercise (see above)
• aspirin 81 mg QD

• recommended for for men > 50 & women > 60 years with at least one cardiovascular risk factor without contraindications [3,59,60]
• optional for elderly diabetics without risk factors
• recommended for younger patients at high risk [60]
• may not diminish cardiovascular risk [41]

• no significant difference in mortality or major cardiovascular events between:

• patients undergoing revascularization & those undergoing medical therapy [50]
• strategies of insulin sensitization (mostly metformin &/or thiazolidinedione) vs insulin provision [50]

• obesity
• hypertension (also see hypertension & diabetes)

• ACE inhibitors reduce proteinuria ( diabetic nephropathy)
• angiotensin II receptor antagonists do NOT reduce proteinuria (see diabetic nephropathy)
• thiazide diuretics recommended as 1st line agents [11]
• carvedilol

• less tendency to cause hyperglycemia & dyslipidemia than other beta blockers
• may reduce risk of microalbuminuria [23]

• target BP is < 130/80 but this is not supported by data

• stricter guidelines < 120/70 mmg Hg [7] not widely accepted
• < 135/80 mm Hg ( [11])
• no benefit to target systolic blood pressure lower than standard therapy (< 140 mm Hg) see ACCORD trial
• INVEST trial results similar to ACCORD trial [61]
• see hypertension & diabetes

• obstructive sleep anea - CPAP may improve glycemic control (see nasal CPAP)
• pain from inflammatory disorders ( osteoarthritis etc)

• salsalate is an anti-inflammatory agent that lowers HgbA1c

• vaccinations:

• hepatitis B vaccine

• diabetics age 19-59 years ASAP after diagnosis [71]
• diabetics age >= 60 years optional [71]

• exacerbations/episodes of hyperglycemia

• rule out infection, especially urinary tract infection in the elderly

• bariatric surgery

• may improve glycemic control in obese patients [76]
• outperforms medical therapy in obese patients [77]

• patient education

• finger stick capillary glucose technique

• preprandial target of 80-120 mg/dL

• factors influencing blood sugar
• signs & symptoms of hypoglycemia
• glucagon IM if found unresponsive (friends & family)
• foot care
• wine 1 glass/day with dinner may diminish fasting blood glucose [38]
• group sessions ineffective [80]
• peer mentoring lowers HbA1c levels by ~1% [81]

• assessment of disease progression

• hemoglobin A1c every 2-3 months
• urinary albumin/creatinine ratio annually
• fasting lipid panel annually
• eye exam

• ophthalmologic evaluation after 5 years of disease
• fundoscopic examination every 6-12 months

• foot care

• inspect feet for deformity, ulceration, vascular insufficiency every 6 months
• deep tendon reflex at ankles
• vibratory & light pressure thresholds in feet

• routine cardiac stress testing not indicated [3]

• multidisciplinary, intensive management improves outcomes [9,10]
• self-monitoring of blood glucose fails to lower HgbA1c the clinically relevant threshold of 0.5% [75]
• intensive therapy has its limits (see ACCORD trial, ADVANCE trial & UKPDS data [40])
• screening of high-risk individuals [10]
• lifestyle modification for prevention [24]
• also see fasting with diabetes mellitus

More General Terms

• diabetes mellitus

Additional Terms

• diabetic amyotrophy/lumbar polyradiculopathy; diabetic lumbosacral radiculoplexus neuropathy (DLRPN)
• diabetic foot
• diabetic gastroparesis
• diabetic nephropathy (diabetic glomerulosclerosis, DMN)
• diabetic polyneuropathy
• diabetic retinopathy (DR, proliferative {PDR} & non-proliferative)
• diabetic teeth & gum problems
• diabetics who become pregnant
• dietary therapy for diabetes mellitus
• fasting with diabetes mellitus
• hyperglycemic-hyperosmolar syndrome; hyperglycemic-hyperosmolar nonketotic coma (HHNC)
• hypertension & diabetes
• hypoglycemic agent
• immune dysfunction in diabetes mellitus
• impotence in diabetics
• insulin resistance
• risk factors for coronary artery disease in patients with diabetes mellitus type-2
• risk factors for diabetes mellitus type 2
• screening for diabetes mellitus type 2
• use of HMG CoA reductase inhibitors (statins) in patients with diabetes mellitus

Internet Database

OMIM: 125851
OMIM: 125853
OMIM: 138190
OMIM: 147670
OMIM: 138079
OMIM: 176730

References

1. Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 629-31
2. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 54
3. Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 15, American College of Physicians, Philadelphia 1998, 2006, 2009
4. Journal Watch 21(3):21, 2001 Mogensen CE et al Randomised controlled trial of dual blockade of renin-angiotensin system in patients with hypertension, microalbuminuria, and non-insulin dependent diabetes: the candesartan and lisinopril microalbuminuria (CALM) study. BMJ 321:1440, 2000 PMID: &dopt=Abstract
5. Genova, A, UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
6. Lee, A. UCLA Multicampus Program in Geriatrics & Gerontology, weekly lecture series, Feb 14, 2002
7. Dhanani, S, GRECC WLA, 6/19/02, personal communication
8. Journal Watch 22(17):132, 2002 Miles JM et al Effect of orlistat in overweight and obese patients with type 2 diabetes treated with metformin. Diabetes Care 25:1123, 2002 PMID: &dopt=Abstract
9. Journal Watch 23(5):37, 2003 Gaede P et al Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med 348:383, 2003 PMID: [1]
10. Prescriber's Letter 10(3):16 2003 a) Screening for Type 2 Diabetes Mellitus in Adults Detail-Document#: [2] b) Summary of 2003 American Diabetes Association Recommendations Detail-Document#: [3] (subscription needed) [4]
11. Journal Watch 23(10):78, 2003 Berl T et al, Cardiovascular outcomes in the Irbesartan Diabetic Nephropathy Trial of patients with type 2 diabetes and overt nephropathy. Ann Intern Med 138(Apr 1):542, 2003 <PubMed> PMID: [5] <Internet> [6]
    - Vijan S & Hayward RA, Treatment of hypertension in type 2 diabetes mellitus: blood pressure goals, choice of agents, and setting priorities in diabetes care. Ann Intern Med 138(Apr 1):593, 2003 <PubMed> PMID: [7] <Internet> [8]
12. Statin Therapy for Patients with Diabetes Prescriber's Letter 10(7):38 2003 Detail-Document#: [9] (subscription needed) [10]
13. Journal Watch 23(23):185, 2003 Riddle MC et al The treat-to-target trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients. Diabetes Care 26:3080, 2003 PMID: [11]
14. Journal Watch 24(4):30, 2004 Salazar-Martinez E et al Coffee consumption and risk for type 2 diabetes mellitus. Ann Intern Med 140:1, 2004 PMID: [12]
15. Guidelines for Improving the Care of the Older Person with Diabetes Mellitus, JAGS 51:S265-280, 2003 PMID: [13]
16. Journal Watch 24(11):90-91, 2004 Quinones MJ, Hernandez-Pampaloni M, Schelbert H, Bulnes-Enriquez I, Jimenez X, Hernandez G, De La Rosa R, Chon Y, Yang H, Nicholas SB, Modilevsky T, Yu K, Van Herle K, Castellani LW, Elashoff R, Hsueh WA. Coronary vasomotor abnormalities in insulin-resistant individuals. Ann Intern Med. 2004 May 4;140(9):700-8. PMID: [14]
17. Lipid Control in Diabetes: Review of Clinical Practice Guidelines Prescriber's Letter 11(6):35 2004 Detail-Document#: [15] (subscription needed) [16]
18. Prescriber's Letter 11(8): 2004 Cinnamon for Patients with Type 2 Diabetes Detail-Document#: [17] (subscription needed) [18]
    - Prescriber's Letter 15(3): 2008 Should Patients Use Cinnamon for Type 2 diabetes? Detail-Document#: [19]
    - Khan A et al, Cinnamon improves glucose and lipids of people with type 2 diabetes. Diabetes Care 2003, 26:3215 PMID: [20]
    - Baker WL et al, Effect of cinnamon on glucose control and lipid parameters. Diabetes Care 2008, 31:41 PMID: [21]
19. Journal Watch 24(18):145, 2004 Hippisley-Cox J, Pringle M. Prevalence, care, and outcomes for patients with diet- controlled diabetes in general practice: cross sectional survey. Lancet. 2004 Jul 31;364(9432):423-8. PMID: [22]
20. Journal Watch 24(19):149, 2004 Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HA, Livingstone SJ, Thomason MJ, Mackness MI, Charlton-Menys V, Fuller JH; CARDS investigators. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet. 2004 Aug 21;364(9435):685-96. PMID: [23]
21. Prescriber's Letter 12(1): 2005 Carvedilol: is it a Better Choice in Patients with Diabetes? Detail-Document#: [24] (subscription needed) [25]
22. Journal Watch 25(3):24, 2005 Schernthaner G, Matthews DR, Charbonnel B, Hanefeld M, Brunetti P; Quartet [corrected] Study Group. Efficacy and safety of pioglitazone versus metformin in patients with type 2 diabetes mellitus: a double-blind, randomized trial. J Clin Endocrinol Metab. 2004 Dec;89(12):6068-76. Erratum in: J Clin Endocrinol Metab. 2005 Feb;90(2):746. PMID: [26]
23. Internal Medicine News, April 15, 2005
24. Prescriber's Letter 12(7): 2005 Evidence for Preventing Type 2 Diabetes Detail-Document#: [27] (subscription needed) [28]
25. Tirosh A, Shai I, Tekes-Manova D, Israeli E, Pereg D, Shochat T, Kochba I, Rudich A; Israeli Diabetes Research Group. Normal fasting plasma glucose levels and type 2 diabetes in young men. N Engl J Med. 2005 Oct 6;353(14):1454-62. PMID: [29]
26. Dr. David S. H. Bell, University of Alabama at Birmingham, Canadian Medical Association Journal, January 17, 2006
27. Centers for Disease Control
28. Rosenstock J et al, Triple therapy in type 2 diabetes: Insulin glargine or rosiglitazone added to combination therapy of sulfonylurea plus metform in insulin-naive patients. Diabetes Care 2006; 29:554 PMID: [30]
29. Internal Medicine World Report vol 21, 2006
30. Prescriber's Letter 13(5): 2006 Byetta (Exenatide) for Weight Loss Detail-Document#: [31] (subscription needed) [32]
31. Costa J et al, Efficacy of lipid-lowering drug treatment of diabetic and non-diabetic patients, Meta-analysis of randomized controlled trials. (meta-analysis that did NOT include Field trial) BMJ 2006; 332:1115 PMID: [33]
    - Reckless JPD Diabetes and lipid lowering. Where are we? We're now sure that statins cut cardiovascular risks in type 2 diabetes. BMJ 2006; 332:1103 PMID: [34]
32. Prescriber's Letter 13(11): 2006 American Diabetes Association Treatment Algorithm for Type 2 Diabetes Treatment of Type 2 Diabetes Mellitus Detail-Document#: [35] (subscription needed) [36]
    - Nathan DM, Buse JB, Davidson MB, Heine RJ, Holman RR, Sherwin R, Zinman B. Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2006 Aug;29(8):1963-72. No abstract available. PMID: [37]
33. Kahn SE et al, Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med 2006, 355:2427 PMID: [38]
    - Nathan DM Thiazolidinediones for initial treatment of type 2 diabetes? N Engl J Med 2006, 355:2477 PMID: [39]
34. Mazzone T et al, Effect of pioglitazone compared with glimepiride on carotid intima-media thickness in type 2 diabetes: A randomized trial. JAMA 2006, 296:2572 PMID: [40]
35. Prescriber's Letter 14(1): 2007 Choosing Initial Monotherapy for Type 2 Diabetes: the ADOPT study Detail-Document#: [41] (subscription needed) [42]
36. Prescriber's Letter 14(7): 2007 Stepwise Approach to Selecting Treatments for Type 2 Diabetes Detail-Document#: [43] (subscription needed) [44]
37. Prescriber's Letter 14(9): 2007 Self-monitoring of blood glucose in patients with type 2 diabetes Detail-Document#: [45] (subscription needed) [46]
38. Shai I et al, Glycemic effects of moderate alcohol intake among patients with type 2 diabetes: A muticenter, randomized, clinical intervention trial. Diabetes Care 2007, 30:3011 PMID: [47]
39. 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. 2000 Jun 24;320(7251):1720-3. PMID: [48]
40. Prescriber's Letter 15(8): 2008 COMMENTARY: A1c: How Low Should You Go? GUIDELINES: ADA Position Statement on Standards of Medical Care in Diabetes - 2008 GUIDELINES: CDA Clinical Practice Guidelines on Monitoring Glycemic Control Detail-Document#: [49] (subscription needed) [50]
41. Ogawa H et al, Low-Dose Aspirin for Primary Prevention of Atherosclerotic Events in Patients With Type 2 Diabetes JAMA. 2008 Nov 9. [Epub ahead of print] <PubMed> PMID: [51] <Internet> [52]
42. Prescriber's Letter 15(12): 2008 CHART: Stepwise Approach to Selecting Treatments for Type 2 Diabetes COMMENTARY: Updated Treatment Recommendations for Type 2 Diabetes CHART: Initiation and Adjustment of Insulin Regimens for Type 2 Diabetes GUIDELINES: 2008 ADA Consensus Statement on Management of Hyperglycemia in Type 2 Diabetes Detail-Document#: [53] (subscription needed) [54]
43. Duckworth W et al for the VADT investigators Glucose Control and Vascular Complications in Veterans with Type 2 Diabetes N Engl J Med 2008, December 17, 2008 PMID: [55]
44. Prescriber's Letter 16(2): 2009 COMMENTARY: Low-dose Aspirin Recommendations for Diabetes Patients GUIDELINES: Screening for Type 2 Diabetes Mellitus in Adults GUIDELINES: Canadian Diabetes Association 2008 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada Detail-Document#: [56] (subscription needed) [57]
45. Prescriber's Letter 16(3): 2009
    - Stepwise Approach to Selecting Treatments for Type 2 Diabetes
    - Initiation and Adjustment of Insulin Regimens for Type 2 Diabetes Detail-Document#: [58] (subscription needed) [59]
46. Whitmer RA et al Hypoglycemic Episodes and Risk of Dementia in Older Patients With Type 2 Diabetes Mellitus JAMA 2009;301:1599-1601 PMID: [60]
47. Young LH et al Cardiac Outcomes After Screening for Asymptomatic Coronary Artery Disease in Patients With Type 2 Diabetes The DIAD Study: A Randomized Controlled Trial JAMA. 2009;301(15):1547-1555 PMID: [61]
48. Montori VM et al Glycemic control in type 2 diabetes: time for an evidence- based about face? Annals of Internal Medicine 2009 150(11) June 2 PMID: [62]
49. Leunissen RW et al Timing and Tempo of First-Year Rapid Growth in Relation to Cardiovascular and Metabolic Risk Profile in Early Adulthood. JAMA. 2009;301(21):2234-2242. PMID: [63]
50. Frye RL et al for The BARI 2D Study Group A Randomized Trial of Therapies for Type 2 Diabetes and Coronary Artery Disease N Engl J Med. 2009 Jun 11;360(24):2503-15 PMID: [64]
51. Meinert CL et al A study of the effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes: II. Mortality results. Diabetes 1970; 19:Suppl:789. PMID: [65]
    - Gerstein HC et al Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med 2008 Jun 12; 358:2545 <PubMed> PMID: [66] <Internet> [67]
    - Patel A et al Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med 2008 Jun 12; 358:2560. <PubMed> PMID: [68] <Internet> [69]
    - Duckworth W et al Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med 2009 Jan 8; 360:129. <PubMed> PMID: [70] <Internet> [71]
    - 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 1998 Sep 12; 352:837. PMID: [72]
    - Montori VM and Fernández-Balsells M. Glycemic control in type 2 diabetes: Time for an evidence- based about-face? Ann Intern Med 2009 Jun 2; 150:803. PMID: [73]
    - Lehman R and Krumholz HM. Tight control of blood glucose in long standing type 2 diabetes. BMJ 2009 Apr 18; 338:901. <PubMed> PMID: &dopt=Abstract <Internet> [74]
    - Havas S. The ACCORD trial and control of blood glucose level in type 2 diabetes mellitus: Time to challenge conventional wisdom. Arch Intern Med 2009 Jan 26; 169:150. PMID: [75]
    - Haynes RB and Haynes GA. What does it take to put an ugly fact through the heart of a beautiful hypothesis? Evid Based Med 2009 Jun; 14:68. <PubMed> PMID: [76] <Internet> [77]
52. Esposito K 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 2009 Sep 1; 151:306. PMID: [78]
53. Kelly TN et al. Systematic review: Glucose control and cardiovascular disease in type 2 diabetes. Ann Intern Med 2009 Sep 15; 151:394. PMID: [79]
54. Greenfield S et al Comorbidity Affects the Relationship Between Glycemic Control and Cardiovascular Outcomes in Diabetes. A Cohort Study Ann Intern Med December 15, 2009 151:854-860 <PubMed> PMID: [80] <Internet> [81]
55. Nathan DM The Role of Glycemia Management in the Prevention of Cardiovascular Disease-Starting Over? Ann Intern Med December 15, 2009 151:888-889 PMID: [82] doi:10.1059/0003-4819-151-12-200912150-00010
56. Currie CJ et al Survival as a function of HbA1c in people with type 2 diabetes: a retrospective cohort study Lancet. 2010 Feb 6;375(9713):438-40. Epub 2010 Jan 26. PMID: [83] doi:10.1016/S0140-6736(09)61969-3 [84]
57. Waknine Y FDA Approvals: Fanapt and Cycloset Medscape Medical News [85]
    - Safety and Tolerability Study of Cycloset in Treatment of Type 2 Diabetes ClinicalTrials.gov [86]
    - Prescriber's Letter 18(2): 2011 COMMENTARY: Cycloset: A New Bromocriptine Formulation for Diabetes CHART: Drug Classes for Type 2 Diabetes Detail-Document#: [87] (subscription needed) [88]
58. Prescriber's Letter 17(5): 2010 CHART: Stepwise Approach to Selecting Treatments for Type 2 Diabetes (ADA) CHART: Stepwise Approach to Selecting Treatments for Type 2 Diabetes (AACE) CHART: Drug Classes for Type 2 Diabetes GUIDELINES: Consensus Statement on Management of Hyperglycemia in Type 2 Diabetes (ADA, 2009) GUIDELINES: Consensus Statement on Management of Hyperglycemia in Type 2 Diabetes (AACE/ACE, 2010) Detail-Document#: [89] (subscription needed) [90]
59. Pignone M et al Aspirin for Primary Prevention of Cardiovascular Events in People With Diabetes: A Position Statement of the American Diabetes Association, a Scientific Statement of the American Heart Association, and an Expert Consensus Document of the American College of Cardiology Foundation Circulation. 2010 May 27 <PubMed> PMID: &dopt=Abstract <Internet> [91]
    - Pignone M et al Aspirin for Primary Prevention of Cardiovascular Events in People With Diabetes: A Position Statement of the American Diabetes Association, a Scientific Statement of the American Heart Association, and an Expert Consensus Document of the American College of Cardiology Foundation Diabetes Care. 2010 Jun;33(6):1395-402. No abstract available. PMID: [92]
60. Prescriber's Letter 17(7): 2010 COMMENTARY: Aspirin for Primary Prevention in Patients with Diabetes PATIENT HANDOUT: Aspirin and Your Heart PATIENT HANDOUT SPANISH VERSION: La Aspirina y el Corazón GUIDELINES: Aspirin for Primary Prevention of Cardiovascular Events in People with Diabetes Detail-Document#: [93] (subscription needed) [94]
61. Cooper-DeHoff RM et al Tight Blood Pressure Control and Cardiovascular Outcomes Among Hypertensive Patients With Diabetes and Coronary Artery Disease. JAMA. 2010;304(1):61-68. <PubMed> PMID: [95] <Internet> [96]
62. Church TS et al. Effects of aerobic and resistance training on hemoglobin A1c levels in patients with type 2 diabetes: A randomized controlled trial. JAMA 2010 Nov 24; 304:2253. PMID: [97]
63. Nylen ES, Kokkinos P, Myers J, Faselis C Prognostic effect of exercise capacity on mortality in older adults with diabetes mellitus. J Am Geriatr Soc. 2010 Oct;58(10):1850-4. PMID: &dopt=Abstract
64. Gonzalez-Perez A et al. Acute pancreatitis in association with type 2 diabetes and antidiabetic drugs: A population-based cohort study. Diabetes Care 2010 Dec; 33:2580. PMID: [98]
65. Prescriber's Letter 18(2): 2011 COMMENTARY: Cycloset: A New Bromocriptine Formulation for Diabetes CHART: Drug Classes for Type 2 Diabetes Detail-Document#: [99] (subscription needed) [100]
66. Buse JB et al. Use of twice-daily exenatide in basal insulin-treated patients with type 2 diabetes: A randomized, controlled trial. Ann Intern Med 2011 Jan 18; 154:103 PMID: [101]
    - Nathan DM. Time for clinically relevant comparative effectiveness studies in type 2 diabetes. Ann Intern Med 2011 Jan 18; 154:131 PMID: [102]
67. Gross JL et al Effect of Antihyperglycemic Agents Added to Metformin and a Sulfonylurea on Glycemic Control and Weight Gain in Type 2 Diabetes: A Network Meta-analysis Annals of Internal Medicine May 16, 2011 154:672-679 <PubMed> PMID: [103] <Internet> [104]
68. Schwartz AV et al. Association of BMD and FRAX score with risk of fracture in older adults with type 2 diabetes. JAMA 2011 Jun 1; 305:2184. PMID: [105]
69. Andrews RC et al. Diet or diet plus physical activity versus usual care in patients with newly diagnosed type 2 diabetes: The Early ACTID randomised controlled trial. Lancet 2011 Jun 25 [106]
    - Hu FB. Diet and exercise for new-onset type 2 diabetes? Lancet 2011 Jun 25; [107]
70. Prescriber's Letter 18(12): 2011 CHART: Initiation and Adjustment of Insulin Regimens for Type 2 Diabetes Detail-Document#: [108] (subscription needed) [109]
71. Centers for Disease Control and Prevention Use of Hepatitis B Vaccination for Adults with Diabetes Mellitus: Recommendations of the Advisory Committee on Immunization Practices (ACIP) MMWR December 23, 2011 / 60(50);1709-1711 [110]
72. American College of Physicians
    - Qaseem A, Vijan S, Snow V, Cross JT, Weiss KB, Owens DK; Clinical Efficacy Assessment Subcommittee of the American College of Physicians. Glycemic control and type 2 diabetes mellitus: the optimal hemoglobin A1c targets. A guidance statement from the American College of Physicians. Ann Intern Med. 2007 Sep 18;147(6):417-22. Summary for patients in: Ann Intern Med. 2007 Sep 18;147(6): I52. <PubMed> PMID: [111] <Internet> [112]
73. Qaseem A et al Oral Pharmacologic Treatment of Type 2 Diabetes Mellitus: A Clinical Practice Guideline From the American College of Physicians Annals of Internal Medicine Feb 7, 2012 156(3):218-231 <PubMed> PMID: [113] <Internet> [114]
74. Ruiter R et al. Lower risk of cancer in patients on metformin in comparison with those on sulfonylurea derivatives: Results from a large population-based follow-up study. Diabetes Care 2012 Jan; 35:119 PMID: [115]
75. Farmer AJ et al. Meta-analysis of individual patient data in randomised trials of self monitoring of blood glucose in people with non-insulin treated type 2 diabetes. BMJ 2012 Feb 27; 344:e486 PMID: [116]
76. Schauer PR et al. Bariatric surgery versus intensive medical therapy in obese patients with diabetes. N Engl J Med 2012 Mar 26 <PubMed> PMID: [117] <Internet> [118]
    - Mingrone G et al. Bariatric surgery versus conventional medical therapy for type 2 diabetes. N Engl J Med 2012 Mar 26 <PubMed> PMID: [119] <Internet> [120]
77. Journal Watch: Physician's First Watch Massachusetts Medical Society
    - Leonetti F et al Obesity, Type 2 Diabetes Mellitus, and Other Comorbidities A Prospective Cohort Study of Laparoscopic Sleeve Gastrectomy vs Medical Treatment Arch Surg. Published online April 16, 2012 <PubMed> PMID: [121] <Internet> [122]
78. Inzucchi SE et al Management of Hyperglycemia in Type2 Diabetes: A Patient-Centered Approach Position Statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) Diabetes Care April 19, 2012 <PubMed> PMID: [123] <Internet> [124]
79. Hemmingsen B et al. Comparison of metformin and insulin versus insulin alone for type 2 diabetes: Systematic review of randomised clinical trials with meta-analyses and trial sequential analyses. BMJ 2012 Apr 19; 344:e1771. PMID: [125]
80. Khunti K et al Effectiveness of a diabetes education and self management programme (DESMOND) for people with newly diagnosed type 2 diabetes mellitus: three year follow-up of a cluster randomised controlled trial in primary care BMJ 2012;344:e2333 <PubMed> PMID: [126] <Internet> [127]
    - Snoek FJ Self management education and good professional consultation skills for patients with diabetes BMJ 2012;344:e2673 <PubMed> PMID: [128] <Internet> [129]
81. Long JA et al. Peer mentoring and financial incentives to improve glucose control in African American veterans: A randomized trial. Ann Intern Med 2012 Mar 20; 156:416. PMID: [130]
82. Am I at Risk for Type 2 Diabetes? [131]
83. National Guideline Clearinghouse
    - General
    - American Association of Clinical Endocrinologists medical guidelines for clinical practice for the management of diabetes mellitus. Diabetes and pregnancy. ngc-guideline: [132]
    - American Association of Clinical Endocrinologists medical guidelines for clinical practice for the management of diabetes mellitus. Diabetes management in the hospital setting. ngc-guideline: [133]
    - American Association of Clinical Endocrinologists medical guidelines for clinical practice for the management of diabetes mellitus. Glycemic management. ngc-guideline: [134]
    - American Association of Clinical Endocrinologists medical guidelines for clinical practice for the management of diabetes mellitus. Hypertension management. ngc-guideline: [135]
    - American Association of Clinical Endocrinologists medical guidelines for clinical practice for the management of diabetes mellitus. Lipid management. ngc-guideline: [136]
    - American Association of Clinical Endocrinologists medical guidelines for clinical practice for the management of ngc-guideline: [137]
    - American Association of Clinical Endocrinologists medical guidelines for clinical practice for the management of diabetes mellitus. Nutrition and diabetes. ngc-guideline: [138]
    - American Association of Clinical Endocrinologists medical guidelines for clinical practice for the management of diabetes mellitus. Patient safety in diabetes care. ngc-guideline: [139]
    - American Association of Clinical Endocrinologists medical guidelines for clinical practice for the management of diabetes mellitus. Prevention of type 2 diabetes mellitus. ngc-guideline: [140]
    - American Association of Clinical Endocrinologists medical guidelines for clinical practice for the management of diabetes mellitus. Screening and diagnosis. ngc-guideline: [141]
    - VA/DoD clinical practice guideline for the management of diabetes mellitus ngc-guideline: [142]
    - Diagnosis and management of type 2 diabetes mellitus in adults. Institute for Clinical Systems Improvement ngc-guideline: [143]
    - Management of type 2 diabetes mellitus. (University of Michigan Health System) ngc-guideline: [144]
    - Recommendations for management of diabetes in Vermont. ngc-guideline: [145]
    - Clinical guideline for pharmacological management of type 2 diabetes. (Joslin Diabetes Center) ngc-guideline: [146]
    - Guideline for the care of the older adult with diabetes. Joslin Diabetes Center ngc-guideline: [147]
    - Type 2 diabetes. In: Prevention, detection and treatment of diabetes in adults. 4th edition. International Diabetes Center ngc-guideline: [148]
    - Type 2 diabetes. The management of type 2 diabetes. National Collaborating Centre for Chronic Conditions ngc-guideline: [149]
    - Optimal therapy recommendations for the prescribing and use of second-line therapy for patients with diabetes inadequately controlled on metformin. Canadian Agency for Drugs and Technologies in Health ngc-guideline: [150]
    - Third-line therapy for patients with type 2 diabetes inadequately controlled with metformin and a sulfonylurea. Canadian Agency for Drugs and Technologies in Health ngc-guideline: [151]
    - Liraglutide for the treatment of type 2 diabetes mellitus. National Institute for Health and Clinical Excellence (NICE) ngc-guideline: [152]
    - Oral pharmacologic treatment of type 2 diabetes mellitus: a clinical practice guideline from the American College of Physicians. ngc-guideline: [153]
    - Glycemic (blood sugar) control
    - Glycemic control and type 2 diabetes mellitus: the optimal hemoglobin A1c targets. A guidance statement from the American College of Physicians. ngc-guideline: [154]
    - Guideline for management of postmeal glucose. International Diabetes Federation ngc-guideline: [155]
    - Nutrition
    - Diabetes type 1 and 2 evidence-based nutrition practice guideline for adults. (American Dietetic Association) ngc-guideline: [156]
    - Joslin Diabetes Center & Joslin Clinic clinical nutrition guideline for overweight and obese adults with type 2 diabetes, prediabetes or those at high risk for developing type 2 diabetes. (Joslin Diabetes Center) ngc-guideline: [157]
    - Blood pressure
    - Exercise
    - Screening & Prevention
    - Standards of medical care in diabetes. IV. Prevention/delay of type 2 diabetes. (American Diabetes Association) ngc-guideline: [158]
    - Exercise and type 2 diabetes: American College of Sports Medicine and the American Diabetes Association: joint position statement. ngc-guideline: [159]
    - Insulin
    - Best practice guideline for the subcutaneous administration of insulin in adults with type 2 diabetes ngc-guideline: [160]
    - (1) Best practice guideline for the subcutaneous administration of insulin in adults with type 2 diabetes. (2) For the subcutaneous administration of insulin in adults with type 2 diabetes 2009 supplement. Registered Nurses Association of Ontario (RNAO) ngc-guideline: [161]
    - Laboratory:
    - Diagnosis and management of diabetes mellitus. Laboratory medicine practice guidelines: evidence-based practice for point-of-care testing. National Academy of Clinical Biochemistry ngc-guideline: [162]
84. Department of Veterans Affairs/Department of Defense (VA/DoD)
    - Clinical Practice Guideline for the Management of Diabetes Mellitus (DM) in Primary Care Guideline Summary (37 page Acrobat file) [163]
    - Clinical Practice Guideline for the Management of Diabetes Mellitus in Primary Care Key Points Card (Acrobat file: 2 cards for cut out, OK for 2 slides) [164]
    - Clinical Practice Guideline for the Management of Diabetes Mellitus in Primary Care Pocket Guide (1) (Acrobat file containing pocket guide part 1) [165]
    - Clinical Practice Guideline for the Management of Diabetes Mellitus in Primary Care Pocket Guide (2) (Acrobat file containing pocket guide part 2) [166]
    - Diabetes Mellitus Algorithm D: Core [167]
    - Diabetes Mellitus Algorithm E: Eye Care [168]
    - Diabetes Mellitus Algorithm F: Foot Care [169]
    - Diabetes Mellitus Algorithm G: Glycemic Control [170]
    - Diabetes Mellitus Algorithm M: Self-Management and Education [171]
    - Diabetes Mellitus Algorithm R: Kidney Function [172]
    - Diabetes Mellitus Algorithm S: Screening and Prevention [173]
    - Diabetes Self-Management Health Tips [174]

diabetes mellitus type 2 (insulin-resistant)