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Diabetes mellitus

Last updated: May 11, 2021

Summarytoggle arrow icon

Diabetes mellitus (DM) describes a group of metabolic diseases that are characterized by chronic hyperglycemia (elevated blood glucose levels). The two most common forms are type 1 and type 2 diabetes mellitus. Type 1 is the result of an autoimmune response that triggers the destruction of insulin-producing β cells in the pancreas, and results in an absolute insulin deficiency. Type 2, which is much more common, has a strong genetic component as well as a significant association with obesity and sedentary lifestyles. Type 2 diabetes is characterized by insulin resistance (insufficient response of peripheral cells to insulin) and pancreatic β cell dysfunction (impaired insulin secretion), resulting in relative insulin deficiency. This form of diabetes usually remains clinically undiagnosed for many years. However, abnormal metabolism (prediabetic state or impaired glucose tolerance), which is associated with chronic hyperglycemia, causes microvascular and macrovascular changes that eventually result in cardiovascular, renal, retinal, and neurological complications. In addition, patients with type 2 diabetes mellitus often present with other conditions (e.g. hypertension, dyslipidemia, obesity) that increase the risk of cardiovascular disease (e.g., myocardial infarction). Renal insufficiency is primarily responsible for the reduced life expectancy of patients with DM.

Because of the chronic and progressive nature of type 1 and type 2 diabetes mellitus, a comprehensive treatment approach is necessary. The primary treatment goals for type 2 diabetes are the normalization of glucose metabolism and the management of risk factors (e.g., arterial hypertension). In theory, weight normalization, physical activity, and a balanced diet should be sufficient to prevent the manifestation of diabetes in prediabetic patients or delay the progression of disease in patients with diabetes mellitus. Unfortunately, these general measures alone are rarely successful, and treatment with oral antidiabetic drugs and/or insulin injections is often required for optimal glycemic control. In type 1 diabetes, insulin replacement therapy is essential and patients must learn to coordinate insulin injections and dietary carbohydrates. Patients with both type 1 and type 2 diabetes mellitus require regular self-management training to improve glycemic control, reduce the risk of life-threatening hypoglycemia or hyperglycemia, and prevent diabetic complications.

  • Type 1:
    • ∼ 5% of all patients with diabetes
    • Childhood onset; : typically < 20 years but can occur at any age; peaks at age 4–6 years and 10–14 years
    • Highest prevalence in non-Hispanic whites
  • Type 2:
    • The estimated prevalence in the US is 9.1%.
    • Adult onset: typically > 40 years ; mean age of onset is decreasing
    • Highest prevalence in Hispanics, Native Americans, Asian Americans, African Americans, and Pacific Islanders

References:[1][2][3][4][5]

Epidemiological data refers to the US, unless otherwise specified.

References:[6][7][8][9][10]

Classification according to the WHO and American Diabetes Association (ADA) [11]

Normal insulin physiology

Type 1 diabetes

  1. Genetic susceptibility
  2. Environmental trigger (often associated with previous viral infection)
  3. Autoimmune response with production of autoantibodies, e.g., Anti-glutamic acid decarboxylase antibody (Anti-GAD), that target insulin-producing cells → progressive destruction of insulin-producing β cells in the pancreatic islets by autoreactive T cells → destruction of 80–90% of β cells
  4. Absolute insulin deficiency → elevated blood glucose levels

Type 2 diabetes

Two major mechanisms:

  1. Peripheral insulin resistance
  2. Pancreatic β cell dysfunction

References:[1][6][7][12][13][14]

Type 1 diabetes Type 2 diabetes
Onset
  • Sudden; diabetic ketoacidosis is often the first manifestation
  • Alternatively, children may present with acute illness and classic symptoms (see “Characteristic features” below)
Characteristic features
  • Weight loss; a thin appearance is typical for type 1 diabetic patients

Diabetes mellitus should be suspected in patients with recurrent cellulitis, candidiasis, dermatophyte infections, gangrene, pneumonia (particularly TB reactivation), influenza, genitourinary infections (UTIs), osteomyelitis, and/or vascular dementia.

References:[7][15][16][17]

  • Hyperglycemia: elevated blood glucose levels

Indication for testing Diagnostic criteria
Symptomatic patients
  • Symptoms or signs of diabetes
  • A single random blood glucose level ≥ 200 mg/dL is sufficient for diagnosis.
  • Alternatively, a pathological fasting plasma glucose (FPG) test, oral glucose tolerance test (OGTT) , or hemoglobin A1C (HbA1C) test establishes the diagnosis (see table below)
    • If hyperglycemia is high enough to suggest but not confirm a diagnosis of DM, two similar test results, either from the same sample or from a separate test sample, will confirm the diagnosis.
Asymptomatic patients
  • < 45 years of age who are obese and have one other risk factor for diabetes (see “Etiology” above)
  • > 45 years of age
Results (venous blood plasma) Diabetes mellitus Prediabetes Healthy
Fasting plasma glucose (FPG) in mg/dL (mmol/L) ≥ 126 (≥ 7.0) 100–125 (5.6–6.9) = impaired fasting glucose < 100 (< 5.6)
2-hour glucose value after oral glucose tolerance test (OGTT) in mg/dL (mmol/L) ≥ 200 (≥ 11.1) 140–199 (7.8–11.0) = impaired glucose tolerance < 140 (< 7.8)
Hemoglobin A1C (HbA1c or A1C) in % ≥ 6.5 5.7–6.4 < 5.7

References:[18][19][20]

DM type 1 vs. type 2

Type 1 Type 2
Relative frequency 10–20% 80–90%
Genetics Positive HLA association Negative HLA association; strong genetic predisposition
Pathogenesis Absolute insulin deficiency Insulin resistance
Association with obesity No Yes
Onset Acute decompensation, typically at age < 20 years Gradual; usually at age > 40 years
C-peptide (Insulin) Decreased or absent Initially elevated
Metabolism Unstable Stable
Risk of ketoacidosis High Low
Treatment Insulin therapy Lifestyle changes → oral antidiabetic drugs insulin therapy

Glucagonoma

Somatostatinoma

References:[2][19][21][22][23][24][25]

The differential diagnoses listed here are not exhaustive.

Aspects of treatment Approach

Individual treatment targets

  • Blood glucose control and regular glycemic monitoring: A1C values
  • Weight loss : Type 2 diabetic patients with a BMI of 27–35 benefit from a weight reduction of 5%; in patients with a BMI > 35 kg/m2, weight reduction of > 10% is recommended.
  • Blood pressure control
  • Improved blood lipid profile with statin therapy
  • Low dose aspirin for men > 50 years and women > 60 years with cardiovascular risk factors
Lifestyle modification
  • ↑ Physical activity → ↓ blood glucose and insulin sensitivity
  • Smoking cessation
  • Balanced diet and nutrition
Self-management education
  • DSME/S programs
Medical treatment
Monitoring complications
  • Regular monitoring of weight, abdominal circumference, blood pressure, blood lipids, renal retention parameters (creatinine, electrolytes), injection site in patients receiving insulin therapy
  • Yearly eye exam (type 1: after 5 years with diabetes mellitus or after the age of 11 years); more frequently in patients with abnormal findings or diagnosed retinopathy
  • Annual urine testing for microalbuminuria
  • Foot exam for neuropathy and ulcers; advise patients to wear appropriate footwear and avoid injury
  • Routine screening for psychosocial problems, including signs of depression and cognitive impairment
  • Pneumococcal vaccines

References:[20][26][27][28]

  • HbA1C target for adults: < 7% (53 mmol/mol)
  • The guidelines for the treatment of DM recommend an individualized treatment strategy.
  • If the target A1C is not reached within 3 months with conservative measures (e.g., diet, exercise), the next step in the therapeutic algorithm should be initiated.
Treatment algorithm Description
General measures

Weight reduction, exercise , medical nutrition therapy, self-management education

Monotherapy

The drug of choice is metformin.

Dual therapy
Triple therapy

Add a third oral antidiabetic drug, nightly basal insulin, or injectable GLP-1 receptor agonist

Combination injectable therapy Metformin + basal insulin + mealtime insulin or GLP-1 receptor agonist
Only consider the substitution of drugs in cases in which the drug is not tolerated or side effects occur.

Oral antidiabetic drugs should be avoided in patients undergoing surgery or suffering from severe illness. Instead, insulin therapy should be initiated!

References:[7][20]

Principles of insulin therapy

Total daily requirement of insulin
  • On average, the body requires 40 USP units of insulin daily.
  • 20 units for basic metabolism → basal insulin
  • 20 units for calorie consumption → bolus insulin
Insulin correction factor
  • 1 unit of insulin lowers the blood glucose level by 30–40 mg/dL (1.7–2.2 mmol/L)
Carbohydrate counting
  • 10 g of carbohydrates increases the blood glucose level by 30–40 mg/dL (1.7–2.2 mmol/L).
Insulin-to-carbohydrate ratio
  • On average, 1 unit of insulin is required for 15 g carbs = 1 carb serving (carb unit); however, this varies greatly from patient to patient.
  • Insulin sensitivity fluctuates over the course of a day Insulin-to-carbohydrate ratio changes over the course of a day.
    • Morning hours: 2 units insulin, lunchtime: 1 unit, evening hours: 1.5 units
Type 1 diabetes
Type 2 diabetes

Indications for insulin therapy

Regimens of insulin therapy

Conventional insulin therapy

  • Fixed regimen of insulin injections: usually twice daily injection; of insulin (mixture of 30% regular insulin and 70% intermediate insulin) with self-monitoring of blood glucose levels
  • Advantages: simple regimen, requiring minimal patient education, not very time-consuming
  • Disadvantages: patients must adhere to a rigid diet and exercise plan. Snacks may be required between meals to avoid hypoglycemia.

Intensive insulin therapy

  • The goal is to simulate physiological glucose metabolism by keeping fasting blood glucose levels < 100 mg/dL (5.6 mmol/L) and postprandial blood glucose levels < 140 mg/dL (< 7.8 mmol/L)
  • Intensified conventional therapy
    • Basal-bolus regimen: basal insulin 1–2 times daily, + bolus insulin injection 30–45 minutes before meals; ; adjusted to preprandial blood glucose measurements
    • The bolus insulin dose depends on the preprandial blood glucose level, meal size and time of day
    • Indication: type 1 diabetes; insulin-dependent type 2 diabetes with a high degree of compliance
  • Insulin pump
  • Advantages
    • Optimal glycemic control and reduced risk of complications in patients with good compliance
    • More flexibility in the daily diet and exercise plan
  • Disadvantages
    • Complex and time-consuming therapy; requires frequent blood glucose measurements
    • High risk of hypoglycemia
    • Patients require intensive education and must be motivated and committed.

Basal supported oral therapy (BOT)

Types of insulin (see insulin)

Problems: early-morning hyperglycemia

  • Dawn phenomenon
    • A common problem (especially in young type 1 diabetic patients)
    • Definition: early-morning hyperglycemia; occurs because of the physiological increase of growth hormone levels; in the early morning hours, which stimulates hepatic gluconeogenesis. The subsequent increase in insulin demand cannot be met in insulin-dependent patients, resulting in elevated blood glucose levels in the morning.
    • Treatment: measurement of nocturnal blood glucose levels; before initiating insulin therapy. The long-acting insulin dose may be given later (around 11 p.m.) or increased under careful glycemic control. Treatment with an insulin pump may be considered in children.
  • Somogyi effect
    • Rare
    • Definition: early-morning hyperglycemia because of a counterregulatory secretion of hormones; that is triggered by nocturnal hypoglycemia secondary to an evening insulin injection
    • Treatment: reduction of the evening dose of the long-acting insulin
  • For additional side effects, see insulin.

Conditions that require insulin adjustments

  • Physical activity: decreases insulin by 1–2 units per 20–30 minutes activity
  • Illness, stress, and changes in diet
    • Increase in insulin demand: : many illnesses are associated with elevated blood glucose levels due to an acute stress reaction; . The subsequent increase in insulin demand cannot be met by patients with insulin deficiency. A higher insulin dose is required.
    • Decrease in insulin demand: vomiting and diarrhea lead to decreased glucose uptake, increasing the risk of hypoglycemia.
  • Surgery: ⅓–½ of the usual daily requirement with frequent monitoring

Insulin purging

References:[6][29][30][31][32][33][34][35][36][37][38][39]

Acute
Long-term

Strict glycemic control is crucial in preventing microvascular disease.

Other complications

References:[1][7][40][41][42][43][44][45][46]

We list the most important complications. The selection is not exhaustive.

Diabetic nephropathy is a major cause of end stage renal disease (ESRD).

Microalbuminuria is the earliest clinical sign of diabetic nephropathy. The extent of albuminuria correlates with the risk of cardiovascular disease!

Early antihypertensive treatment delays the progression of diabetic nephropathy!

References:[2][20][48][53][54][55][56][57]

References:[58][59][60][61][62][63]

Distal symmetric polyneuropathy

Autonomic neuropathy

Urogenital system
Cardiovascular system
Gastrointestinal system
Other manifestations

References:[58][64][65][66][67][68][69][70]

Neuropathic diabetic foot Ischemic diabetic foot
Clinical features
  • Warm, dry skin, foot pulses are palpable
  • Cool, pale foot with no palpable pulses
Additional info
  • Prevention
    • Glycemic control
    • Regular foot examinations
    • Self-monitoring and proper foot care
Treatment of foot ulcers

In about ⅓ of patients with diabetic foot, the underlying cause is both ischemic and neuropathic.

References:[67][71][72][73]

References:[7]

Gestational diabetes mellitus Pregestational diabetes mellitus
Definition
Epidemiology
Pathophysiology
  • As for diabetes mellitus type 1 or 2
Risk factors
  • As for diabetes mellitus type 1 or 2
Clinical features
  • As for diabetes mellitus type 1 or 2
Screening and diagnostics
Treatment
  • Glycemic control
  • Regular ultrasound to evaluate fetal development
  • Consider inducing delivery at week 39–40 if glycemic control is poor or if complications occur
  • Stringent glycemic control (exercise, diet, insulin therapy)
  • Delivery and postpartum
    • Consider early delivery if the patient has poor glycemic control or preeclampsia
    • Consider C-section if estimated fetus weight > 4500 g
    • Intrapartum IV insulin and dextrose to avoid blood glucose fluctuations (maintain normoglycemia 80–100 mg/dL; hourly blood glucose measurements
Complications
Prognosis
  • In most cases, gestational diabetes resolves after pregnancy.
  • Increased risk of gestational diabetes recurring in subsequent pregnancies (∼ 50%)
  • Increased risk of developing type 2 diabetes mellitus (up to 50% over 10 years)→ screen for DM 6–12 weeks postpartum (75 g 2-hour GTT); repeat every 3 years
  • As for diabetes mellitus type 1 or 2

References:[3][4][74][75][76][77][78][79]

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  1. Khardori R. Type 2 Diabetes Mellitus. Type 2 Diabetes Mellitus. New York, NY: WebMD. http://emedicine.medscape.com/article/117853-overview#showall. Updated: January 12, 2017. Accessed: February 13, 2017.
  2. American Diabetes Association. Standards of Medical Care in Diabetes—2016 Abridged for Primary Care Providers. Clinical Diabetes. 2016; 34 (1): p.3-21. doi: 10.2337/diaclin.34.1.3 . | Open in Read by QxMD
  3. Khardori R. Type 1 Diabetes Mellitus. Type 1 Diabetes Mellitus. New York, NY: WebMD. http://emedicine.medscape.com/article/117739-overview#a4. Updated: September 30, 2016. Accessed: February 13, 2017.
  4. Delahanty LM, McCulloch DK. Nutritional considerations in type 1 diabetes mellitus. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/nutritional-considerations-in-type-1-diabetes-mellitus?source=search_result&search=carbohydrate%20counting&selectedTitle=2~13.Last updated: April 22, 2016. Accessed: February 13, 2017.
  5. How to calculate an insulin-to-carb ratio. http://www.bd.com/us/diabetes/page.aspx?cat=7001&id=7303. . Accessed: February 13, 2017.
  6. Insulin Management of Type 2 Diabetes Mellitus. http://www.aafp.org/afp/2011/0715/p183.html. Updated: July 15, 2011. Accessed: February 13, 2017.
  7. Medscape. Insulin regular human (Rx, OTC). Insulin regular human (Rx, OTC). New York, NY: WebMD. http://reference.medscape.com/drug/humulin-r-novolin-r-insulin-regular-human-999007. . Accessed: February 13, 2017.
  8. McCulloch DK. Insulin therapy in type 2 diabetes mellitus. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/insulin-therapy-in-type-2-diabetes-mellitus?source=search_result&search=diabetes%20mellitus%20treatment&selectedTitle=7~150.Last updated: October 26, 2016. Accessed: February 13, 2017.
  9. McCulloch DK. Management of persistent hyperglycemia in type 2 diabetes mellitus. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/management-of-persistent-hyperglycemia-in-type-2-diabetes-mellitus?source=search_result&search=persistent%20hyperglycemia&selectedTitle=1~150.Last updated: January 18, 2017. Accessed: February 14, 2017.
  10. American Diabetes Association. Standards of Medical Care in Diabetes - 2015. Diabetes Care. 2015; 38 (Suppl. 1). doi: 10.2337/dc15-S001 . | Open in Read by QxMD
  11. McCulloch DK. Management of blood glucose in adults with type 1 diabetes mellitus. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/management-of-blood-glucose-in-adults-with-type-1-diabetes-mellitus?source=search_result&search=insulin%20pump&selectedTitle=1~81#H12.Last updated: October 19, 2016. Accessed: February 13, 2017.
  12. McCulloch DK. Cases Illustrating Problems with Insulin Therapy for Diabetes Mellitus. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/cases-illustrating-problems-with-insulin-therapy-for-diabetes-mellitus.Last updated: July 27, 2017. Accessed: January 19, 2018.
  13. Cooperman M. Somogyi Phenomenon. In: Griffing GT, Somogyi Phenomenon. New York, NY: WebMD. https://emedicine.medscape.com/article/125432-overview. Updated: September 28, 2016. Accessed: January 19, 2018.
  14. Colton PA, Olmsted MP, Daneman D, et al. Eating Disorders in Girls and Women With Type 1 Diabetes: A Longitudinal Study of Prevalence, Onset, Remission, and Recurrence. Diabetes Care. 2015; 38 (7): p.1212-1217. doi: 10.2337/dc14-2646 . | Open in Read by QxMD
  15. Tervaert TWC, Mooyaart AL, Amann K, et al. Pathologic Classification of Diabetic Nephropathy. Journal of the American Society of Nephrology. 2010; 21 (4): p.556-563. doi: 10.1681/asn.2010010010 . | Open in Read by QxMD
  16. Alsaad KO, Herzenberg AM. Distinguishing diabetic nephropathy from other causes of glomerulosclerosis: an update. J Clin Pathol. 2007; 60 (1): p.18-26. doi: 10.1136/jcp.2005.035592 . | Open in Read by QxMD
  17. DIABETIC NEPHROPATHY. https://www.kidneypathology.com/English_version/Diabetes_and_others.html. . Accessed: June 11, 2019.
  18. Moosa MR, Van der Walt I, Naicker S, Meyers AM. Important causes of chronic kidney disease in South Africa. South African Medical Journal. 2015 .
  19. Fried LF, Emanuele N, Zhang JH, Brophy M, Conner TA, Duckworth W, Leehey DJ, McCullough PA, O'Connor T, Palevsky PM, Reilly RF, Seliger SL, Warren SR, Watnick S, Peduzzi P, Guarino P. Combined Angiotensin Inhibition for the Treatment of Diabetic Nephropathy. New England Journal of Medicine. 2013 .
  20. Diabetic Nephropathy Workup. https://emedicine.medscape.com/article/238946-workup. Updated: March 13, 2018. Accessed: June 11, 2019.
  21. Agabegi SS, Agabegi ED. Step-Up To Medicine. Wolters Kluwer Health ; 2015
  22. Bakris GL. Mechanisms of glomerular hyperfiltration in diabetes mellitus. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/mechanisms-of-glomerular-hyperfiltration-in-diabetes-mellitus?source=see_link.Last updated: May 26, 2015. Accessed: February 14, 2017.
  23. Bakris GL. Overview of diabetic nephropathy. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/overview-of-diabetic-nephropathy?source=see_link.Last updated: November 15, 2016. Accessed: February 14, 2017.
  24. Batuman V. Diabetic Nephropathy. Diabetic Nephropathy. New York, NY: WebMD. http://emedicine.medscape.com/article/238946-clinical. Updated: September 30, 2016. Accessed: February 14, 2017.
  25. Bakris GL. Treatment of diabetic nephropathy. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/treatment-of-diabetic-nephropathy?source=see_link.Last updated: December 7, 2016. Accessed: February 14, 2017.
  26. Bakris GL. Treatment of hypertension in patients with diabetes mellitus. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/treatment-of-hypertension-in-patients-with-diabetes-mellitus?source=see_link.Last updated: December 14, 2016. Accessed: February 14, 2017.
  27. Agabegi SS, Agabegi ED. Step-Up To Medicine. Lippincott Williams & Wilkins ; 2013
  28. Fraser CE, D'Amico DJ. Diabetic retinopathy: Classification and clinical features. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/diabetic-retinopathy-classification-and-clinical-features?source=search_result&search=diabetic%20retinopathy&selectedTitle=1~132#H14.Last updated: October 28, 2016. Accessed: February 14, 2017.
  29. Common Eye Disorders. https://www.cdc.gov/visionhealth/basics/ced/index.html. Updated: September 29, 2015. Accessed: February 14, 2017.
  30. Bhavsar AR. Diabetic Retinopathy. Diabetic Retinopathy. New York, NY: WebMD. http://emedicine.medscape.com/article/1225122-overview#showall. Updated: July 31, 2016. Accessed: February 14, 2017.
  31. Fraser CE, D'Amico DJ. Diabetic retinopathy: Prevention and treatment. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/diabetic-retinopathy-prevention-and-treatment?source=search_result&search=diabetic%20retinopathy&selectedTitle=2~132.Last updated: September 28, 2016. Accessed: February 14, 2017.
  32. Fong DS, Aiello L, Gardner TW, et al. Retinopathy in Diabetes. Diabetes Care. 2003; 27 (Supplement 1): p.S84-S87. doi: 10.2337/diacare.27.2007.s84 . | Open in Read by QxMD
  33. Feldman EL, McCulloch DK. Treatment of diabetic neuropathy. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/treatment-of-diabetic-neuropathy?source=see_link.Last updated: January 9, 2017. Accessed: February 14, 2017.
  34. Feldman EL. Epidemiology and classification of diabetic neuropathy. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/epidemiology-and-classification-of-diabetic-neuropathy?source=search_result&search=diabetes%20mellitus%20treatment&selectedTitle=18~150.Last updated: March 16, 2015. Accessed: February 14, 2017.
  35. Quan D. Diabetic Neuropathy. Diabetic Neuropathy. New York, NY: WebMD. http://emedicine.medscape.com/article/1170337-clinical#showall. Updated: July 6, 2016. Accessed: February 14, 2017.
  36. McCulloch DK. Evaluation of the diabetic foot. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/evaluation-of-the-diabetic-foot?source=search_result&search=diabetic%20foot&selectedTitle=2~58.Last updated: January 6, 2017. Accessed: February 14, 2017.
  37. Bril V, Franklin GM, Backonja M, et al. Evidence-based guideline: Treatment of painful diabetic neuropathy. Neurology. 2011; 76 (20): p.1758-1765. doi: 10.1212/WNL.0b013e3182166ebe . | Open in Read by QxMD
  38. Ang L, Jaiswal M, Martin C, Pop-Busui R. Glucose Control and Diabetic Neuropathy: Lessons from Recent Large Clinical Trials. Curr Diab Rep. 2014; 14 (9): p.528. doi: 10.1007/s11892-014-0528-7 . | Open in Read by QxMD
  39. Snyder MJ, Gibbs LM, Lindsay TJ. Treating Painful Diabetic Peripheral Neuropathy: An Update.. Am Fam Physician. 2016; 94 (3): p.227-34.
  40. Bronze MS. Diabetic Foot Infections. Diabetic Foot Infections. New York, NY: WebMD. http://emedicine.medscape.com/article/237378-overview#a4. Updated: August 4, 2016. Accessed: February 14, 2017.
  41. Weintrob AC, Sexton DJ. Clinical manifestations, diagnosis, and management of diabetic infections of the lower extremities. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/clinical-manifestations-diagnosis-and-management-of-diabetic-infections-of-the-lower-extremities?source=see_link.Last updated: February 14, 2017. Accessed: February 14, 2017.
  42. Armstrong DG, de Asla RJ, McCulloch DK. Management of diabetic foot ulcers. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/management-of-diabetic-foot-ulcers?source=see_link.Last updated: January 27, 2017. Accessed: February 14, 2017.
  43. Kasper DL, Fauci AS, Hauser SL, Longo DL, Lameson JL, Loscalzo J. Harrison's Principles of Internal Medicine. McGraw-Hill Education ; 2015
  44. Le T, Bhushan V, Chen V, King M. First Aid for the USMLE Step 2 CK. McGraw-Hill Education ; 2015
  45. Jenkins B, McInnis M, Lewis C. Step-Up to USMLE Step 2 CK. Lippincott Williams & Wilkins ; 2015
  46. Diabetes Country Profiles, 2016 - United States Of America.
  47. Krzewska A, Ben-Skowronek I. Effect of Associated Autoimmune Diseases on Type 1 Diabetes Mellitus Incidence and Metabolic Control in Children and Adolescents. Biomed Res Int. 2016; 2016 : p.1-12. doi: 10.1155/2016/6219730 . | Open in Read by QxMD
  48. Thorn LM, Forsblom C, Waden J, et al. Effect of Parental Type 2 Diabetes on Offspring With Type 1 Diabetes. Diabetes Care. 2008; 32 (1): p.63-68. doi: 10.2337/dc08-0472 . | Open in Read by QxMD
  49. Elsayed EF, Tighiouart H, Weiner DE, et al. Waist-to-hip ratio and body mass index as risk factors for cardiovascular events in CKD. Am J Kidney Dis. 2008; 52 (1): p.49-57. doi: 10.1053/j.ajkd.2008.04.002 . | Open in Read by QxMD
  50. American Diabetes Association. 2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes—2020. Diabetes Care. 2019; 43 (Supplement 1): p.S14-S31. doi: 10.2337/dc20-s002 . | Open in Read by QxMD
  51. McCulloch DK, Robertson RP. Pathogenesis of type 2 diabetes mellitus. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/pathogenesis-of-type-2-diabetes-mellitus?source=see_link.Last updated: November 17, 2016. Accessed: February 13, 2017.
  52. Draznin B. Molecular mechanisms of insulin resistance: Serine phosphorylation of insulin receptor substrate-1 and increased expression of p85 : The two sides of a coin. Diabetes. 2006; 55 (8): p.2392-2397. doi: 10.2337/db06-0391 . | Open in Read by QxMD
  53. Whittaker J. Structure and Function of the Insulin Receptor. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/structure-and-function-of-the-insulin-receptor.Last updated: April 24, 2018. Accessed: January 12, 2019.
  54. Miller JH. Acanthosis Nigricans. In: James WD, Acanthosis Nigricans. New York, NY: WebMD. http://emedicine.medscape.com/article/1102488-clinical#b5. Updated: September 23, 2016. Accessed: August 23, 2016.
  55. Levitsky LL, Misra M. Epidemiology, presentation, and diagnosis of type 1 diabetes mellitus in children and adolescents. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/epidemiology-presentation-and-diagnosis-of-type-1-diabetes-mellitus-in-children-and-adolescents?source=search_result&search=diabetes%20mellitus&selectedTitle=4~150.Last updated: March 15, 2016. Accessed: February 13, 2017.
  56. Skin Complications. http://www.diabetes.org/living-with-diabetes/complications/skin-complications.html?referrer=https://www.google.ca/. Updated: March 31, 2014. Accessed: February 13, 2017.
  57. McCulloch DK. Clinical presentation and diagnosis of diabetes mellitus in adults. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/clinical-presentation-and-diagnosis-of-diabetes-mellitus-in-adults?source=see_link.Last updated: January 20, 2017. Accessed: February 13, 2017.
  58. Elhomsy G. C-Peptide . C-Peptide . New York, NY: WebMD. http://emedicine.medscape.com/article/2087824-overview#a2. Updated: December 4, 2014. Accessed: February 13, 2017.
  59. Le T, Bhushan V, Sochat M, Petersen M, Micevic G, Kallianos K. First Aid for the USMLE Step 1 2014. McGraw-Hill Medical ; 2014
  60. Bergsland E. Glucagonoma and the glucagonoma syndrome. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/glucagonoma-and-the-glucagonoma-syndrome?source=search_result&search=glucagonoma&selectedTitle=1~22.Last updated: August 10, 2016. Accessed: February 13, 2017.
  61. Santacroce L. Glucagonoma. Glucagonoma. New York, NY: WebMD. http://emedicine.medscape.com/article/118899-overview#showall. Updated: May 14, 2015. Accessed: February 13, 2017.
  62. Patterson JW. Practical Skin Pathology: A Diagnostic Approach. Elsevier Health Sciences ; 2013
  63. Bergsland E, Nathan DM, Whitcomb DC, Grover S. Somatostatinoma: Clinical Manifestations, Diagnosis, and Management. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/somatostatinoma-clinical-manifestations-diagnosis-and-management.Last updated: December 12, 2017. Accessed: June 13, 2018.
  64. Aspirin. http://www.diabetes.org/living-with-diabetes/treatment-and-care/medication/other-treatments/aspirin.html?referrer=https://www.google.de/. Updated: May 13, 2014. Accessed: February 13, 2017.
  65. Armstrong C. Updated Recommendations on Daily Aspirin Use in Patients with Diabetes. Am Fam Physician. 2010; 82 (12): p.1559-1563.
  66. McCulloch DK, Robertson P. Prevention of Type 2 Diabetes Mellitus. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/prevention-of-type-2-diabetes-mellitus.Last updated: January 8, 2018. Accessed: January 19, 2018.
  67. McCulloch DK. Diabetic retinopathy: Pathogenesis. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/diabetic-retinopathy-pathogenesis?source=search_result&search=diabetic%20retinopathy&selectedTitle=3~132.Last updated: January 23, 2017. Accessed: February 14, 2017.
  68. Cherqaoui R, McKenzie S, Nunlee-Bland G. Diabetic Cheiroarthropathy: A Case Report and Review of the Literature. Case Rep Endocrinol. 2013; 2013 . doi: 10.1155/2013/257028 . | Open in Read by QxMD
  69. Upreti V, Vasdev V, Dhull P, Patnaik SK. Prayer sign in diabetes mellitus. Indian J Endocrinol Metab. 2013; 17 (4): p.769-770. doi: 10.4103/2230-8210.113784 . | Open in Read by QxMD
  70. Cox GM. Mucormycosis (zygomycosis). In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/mucormycosis-zygomycosis?source=search_result&search=zygomycosis&selectedTitle=1~69.Last updated: January 25, 2017. Accessed: February 14, 2017.
  71. Crum-Clanflone NF. Mucormycosis. Mucormycosis. New York, NY: WebMD. http://emedicine.medscape.com/article/222551-overview#showall. Updated: April 3, 2015. Accessed: February 14, 2017.
  72. Micheletti RG, Fishbein GA, Currier JS, Fishbein MC. Mönckeberg sclerosis revisited: a clarification of the histologic definition of Mönckeberg sclerosis.. Arch Pathol Lab Med. 2008; 132 (1): p.43-7. doi: 10.1043/1543-2165(2008)132[43:MSRACO]2.0.CO;2 . | Open in Read by QxMD
  73. Barnes CJ. Necrobiosis Lipoidica. In: Griffing GT, Necrobiosis Lipoidica. New York, NY: WebMD. https://emedicine.medscape.com/article/1103467. Updated: February 26, 2017. Accessed: January 19, 2018.
  74. Le T, Bhushan V, Bagga HS. First Aid for the USMLE Step 2 CK. McGraw-Hill Medical ; 2009
  75. Moore TR. Diabetes Mellitus and Pregnancy . In: Griffing GT, Diabetes Mellitus and Pregnancy . New York, NY: WebMD. http://emedicine.medscape.com/article/127547. Updated: June 16, 2016. Accessed: February 13, 2017.
  76. Baur AR. Macrosomia. In: Isaacs C, Macrosomia. New York, NY: WebMD. http://emedicine.medscape.com/article/262679. Updated: February 3, 2017. Accessed: February 14, 2017.
  77. Riskin A, Garcia-Prats JA. Infant of a Diabetic Mother. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/infant-of-a-diabetic-mother.Last updated: August 15, 2016. Accessed: February 14, 2013.
  78. Randel A. Practice Guidelines - ACOG Releases Guideline on Gestational Diabetes. Am Fam Physician. 2014; 90 (6): p.416-417.
  79. Caughey AB. Gestational Diabetes Mellitus: Obstetrical Issues and Management. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/gestational-diabetes-mellitus-obstetrical-issues-and-management.Last updated: September 13, 2017. Accessed: January 19, 2018.
  80. Herold G. Internal Medicine. Herold G ; 2014
  81. Prediabetes. http://www.mayoclinic.org/diseases-conditions/prediabetes/diagnosis-treatment/treatment/txc-20270050. Updated: November 22, 2016. Accessed: February 13, 2017.
  82. American Diabetes Association. Classification and Diagnosis of Diabetes. Diabetes Care. 2014; 38 (Supplement_1): p.S8-S16. doi: 10.2337/dc15-s005 . | Open in Read by QxMD
  83. McCulloch DK. Classification of Diabetes Mellitus and Genetic Diabetic Syndromes. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/classification-of-diabetes-mellitus-and-genetic-diabetic-syndrome.Last updated: January 30, 2018. Accessed: October 22, 2018.
  84. Karl A. Metcalfe, Graham A. Hitman, Rachel E. Rowe, Mohammed Hawa, Xiaojian Huang, Timothy Stewart, and R. David G. Leslie. Concordance for Type 1 Diabetes in Identical Twins Is Affected by Insulin Genotype. American Diabetes Association. 2001 .
  85. Poulsen P, Esteller M, Vaag A, Fraga MF.. The Epigenetic Basis of Twin Discordance in Age-Related Diseases. Pediatric Research. 2007 .