Difference between revisions of "Diabetes mellitus type 2 natural history, complications, and prognosis"

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=== COVID-19 infection ===
 
=== COVID-19 infection ===
  
* [[Diabetes mellitus]], specifically [[Diabetes mellitus type 2|type 2 diabetes]] has been recognized as one of the most common [[Comorbidity|comorbidities]] of [[COVID-19]], caused by severe acute respiratory syndrome coronavirus-2 ([[SARS-CoV-2]]). It has been estimated that 20-25% of patients with [[COVID-19]] had diabetes.<ref name="pmid323346462">{{cite journal| author=Bornstein SR, Rubino F, Khunti K, Mingrone G, Hopkins D, Birkenfeld AL | display-authors=etal| title=Practical recommendations for the management of diabetes in patients with COVID-19. | journal=Lancet Diabetes Endocrinol | year= 2020 | volume= 8 | issue= 6 | pages= 546-550 | pmid=32334646 | doi=10.1016/S2213-8587(20)30152-2 | pmc=7180013 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32334646  }}</ref>
+
* [[Diabetes mellitus]], specifically [[Diabetes mellitus type 2|type 2 diabetes]] has been recognized as one of the most common [[Comorbidity|comorbidities]] of [[COVID-19]], caused by [[SARS-CoV-2|severe acute respiratory syndrome coronavirus-2]] ([[SARS-CoV-2]]). It has been estimated that 20-25% of patients with [[COVID-19]] had diabetes.<ref name="pmid323346462">{{cite journal| author=Bornstein SR, Rubino F, Khunti K, Mingrone G, Hopkins D, Birkenfeld AL | display-authors=etal| title=Practical recommendations for the management of diabetes in patients with COVID-19. | journal=Lancet Diabetes Endocrinol | year= 2020 | volume= 8 | issue= 6 | pages= 546-550 | pmid=32334646 | doi=10.1016/S2213-8587(20)30152-2 | pmc=7180013 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32334646  }}</ref>
 
*[[SARS-CoV-2]] infection has been linked with higher rate of hospitalization and [[mortality]] in diabetic patients compared to non-diabetics.  
 
*[[SARS-CoV-2]] infection has been linked with higher rate of hospitalization and [[mortality]] in diabetic patients compared to non-diabetics.  
 
*Records from the [[Centers for Disease Control and Prevention]] ([[Centers for Disease Control and Prevention|CDC]]) and other national health centers and hospitals state that diabetic patients with [[COVID-19]] have up to 50% higher chance of death compared to non diabetics with this infection.<ref name="pmid32178769">{{cite journal| author=Remuzzi A, Remuzzi G| title=COVID-19 and Italy: what next? | journal=Lancet | year= 2020 | volume= 395 | issue= 10231 | pages= 1225-1228 | pmid=32178769 | doi=10.1016/S0140-6736(20)30627-9 | pmc=7102589 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32178769  }}</ref>
 
*Records from the [[Centers for Disease Control and Prevention]] ([[Centers for Disease Control and Prevention|CDC]]) and other national health centers and hospitals state that diabetic patients with [[COVID-19]] have up to 50% higher chance of death compared to non diabetics with this infection.<ref name="pmid32178769">{{cite journal| author=Remuzzi A, Remuzzi G| title=COVID-19 and Italy: what next? | journal=Lancet | year= 2020 | volume= 395 | issue= 10231 | pages= 1225-1228 | pmid=32178769 | doi=10.1016/S0140-6736(20)30627-9 | pmc=7102589 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32178769  }}</ref>

Latest revision as of 20:10, 2 August 2020

Diabetes mellitus main page

Diabetes mellitus type 2 Microchapters

Home

Patient information

Overview

Historical Perspective

Pathophysiology

Causes

Differentiating Diabetes Mellitus Type 2 from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

Chest X Ray

CT

MRI

Echocardiography or Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical therapy

Life Style Modification
Pharmacotherapy
Glycemic Control

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Seyedmahdi Pahlavani, M.D. [2]Anahita Deylamsalehi, M.D.[3]"

Overview

If diabetes mellitus type 2 is left untreated, it may result in hyperosmolar hyperglycemic state (HHS) and in rare circumstances, diabetic ketoacidosis (DKA). These are classified as acute complications of diabetes. Chronic complications of diabetes mellitus include microvascular and macrovascular complications. Early diagnosis and prompt treatment of these complications may result in improved prognosis and less long term morbidity and mortalities.

Natural History

Type 2 diabetes may go unnoticed for years because symptoms are typically mild, non-existent or sporadic, and usually there are no ketoacidotic episodes. However, severe long-term complications can result from unnoticed type 2 diabetes, including renal failure due to diabetic nephropathy, vascular disease (including coronary artery disease), visual changes due to diabetic retinopathy, loss of sensation or pain due to diabetic neuropathy, and liver damage from non-alcoholic steatohepatitis secondary to metabolic syndrome.
Untreated DM type 2 may also result in acute complications such as hyperosmolar hyperglycemic state (HHS) and in rare circumstances, diabetic ketoacidosis (DKA).

Complications

Complications of diabetes mellitus type 2 are divided in to 2 major groups:[1] [2][3][4][5]

Acute complications

Acute complications include diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS). These complications are seen in type 2 diabetes but HHS is more common and usually is seen in old age with limited therapeutic resources.

Chronic complications

The following table summarizes the chronic complications of diabetes.

Chronic complications of Diabetes
Type Organ system Compliaction
Microvascular complications Eye
Nervous system
Kidneys
  • Nephropathy (albuminuria and declining renal function)
Macrovascular complications Coronary and vascular
CNS
Others Gastrointestinal (GI)
Genitourinary
HEENT
Skin
Eye
CNS
  • Unlike Type 1 diabetes, there is little tendency toward ketoacidosis in Type 2 diabetes, though it is not unknown. One effect that can occur is non ketotic hyperglycemia. Complex and multi-factorial metabolic changes lead to damage and function impairment of many organs, most importantly the cardiovascular system in both types. This leads to substantially increased morbidity and mortality in both Type 1 and Type 2 patients, but the two have quite different origins and treatments despite the similarity in complications.
  • Type 2 diabetes has been related to reduction in verbal fluency and memory in a period of ~ 5 years. Furthermore type 2 diabetes is related to earlier onset of dementia. Ten years follow up of diabetic patients in their midlife demonstrated rapid decline in global cognitive function, executive function and processing speed compared to normal population. Diabetic patients have higher chance of earlier onset of brain atrophy, included hippocampal and medial temporal atrophy.[7]

Heart Disease and Stroke

Kidney Disease

  • South Asian population are more prone to develop diabetic nephropathy, compared to the Caucasian population.[11]
  • In a study done in China, 21.3% of diabetic patients developed chronic kidney disease.[12]
  • There are some data suggesting that there is a faster rate of renal function deterioration in diabetic kidney disease (DKD) or diabetic kidney disease (DKD) superimposed on nondiabetic renal disease (NDRD), compared to nondiabetic renal disease.[13]
  • There is a possible relationship between polymorphisms within the Carnosine Dipeptidase 1 (CNDP1) gene and diabetic nephropathy development.[14]
  • Diabetes can damage the filtering ability of kidneys. High levels of blood sugar make the kidneys filter too much blood. All this extra work is hard on the filters. After many years, they start to leak. Useful protein is lost in the urine. Having small amounts of protein in the urine is called microalbuminuria. When kidney disease is diagnosed early, (during microalbuminuria), several treatments may keep kidney disease from getting worse. Having larger amounts is called macroalbuminuria. When kidney disease is caught later (during macroalbuminuria), end-stage renal disease (ESRD) usually follows. In time, the stress of overwork causes the kidneys to lose their filtering ability. Waste products then start to build up in the blood. Finally, the kidneys fail. This failure, ESRD, is very serious. A person with ESRD needs to have a kidney transplant or to have the blood filtered by machine (dialysis). Diabetic kidney disease can be prevented by keeping blood sugar in the target range.
  • A study done on Chinese population found an association between elevated tyrosine level and increased likelihood of diabetic nephropathy.[15]
  • There are some data that support uNCR (urinary neutrophil gelatinase-associated lipocalin (uNGAL)/Cr ratio) as a possible diagnostic tool for suspected diabetic kidney disease or in patients that required confirmatory kidney biopsy. Based on these data, diabetic patients with uNCR ratio more than 60.685 ng/mg has 7.595 times higher probability of nephrotic-range proteinuria compared to the group with uNCR≤60.685 ng/mg.[16]

Eye Complications

  • People with diabetes are 40% more likely to suffer from glaucoma than people without diabetes.[17] The duration of diabetes is directly related to higher risk of glaucoma development. Thus risk also increases with age. Glaucoma occurs when pressure builds up in the eye, and vision is gradually lost because the retina and nerve are damaged.
  • Many people without diabetes get cataracts, but people with diabetes are 60% more likely to develop this eye condition. People with diabetes also tend to get cataracts at a younger age and have them progress faster.[18] With cataracts, there is clouding of the clear lens of the eye, which blocks light.
  • Diabetic retinopathy is a general term for all disorders of the retina caused by diabetes. In nonproliferative retinopathy, capillaries in the back of the eye balloon and form pouches. Nonproliferative retinopathy can move through three stages (mild, moderate, and severe), as more and more blood vessels become blocked. In some people, retinopathy progresses after several years to a more serious form, called proliferative retinopathy which can lead to blindness caused by retinal detachment. People who keep their blood sugar levels closer to normal are less likely to have retinopathy or have milder forms.[19]
  • A study done on hospitalized diabetic patients showed that rapid HbA1c reduction is related to higher chance of proliferative retinopathy, while gradual decrease is safe.[20]
  • A cross-sectional study demonstrated a positive association between retinopathy development and myostatin level in diabetic patients.[21]
  • Prevention of severe hypoglycemia, smoking cessation and maintaining renal function have been introduced as factors that prevent visual loss in diabetic patients.[22]
  • Apoptosis of retinal pigmented epithelial cells (RPEs) is one of the possible mechanisms of diabetic retinopathy development. A molecule named miR-203a-3p has been recognized as an important regulator of CoCl2-induced RPEs apoptosis. Deregulation of this molecule may serve as a path for limiting diabetic retinopathy.[23]
  • Recommendations for ophthalmologic screening is at the time of diagnosis and then yearly in the presence of retinopathy. Otherwise, ophthalmologic examinations can be done every 2 years if there is no sign of retinopathy.[1]

Diabetic Neuropathy and Nerve Damage

  • People with diabetes can also have what is called focal neuropathy. In this kind of nerve damage, a nerve or a group of nerves is affected, causing sudden weakness or pain. It can lead to double vision, a paralysis on one side of the face called Bell's palsy, or pain in the front of the thigh or other parts of the body.
  • People with diabetes also are at risk for compressed nerves. Carpal tunnel syndrome is a common cause of numbness and tingling in the fingers and can lead to muscle pain and weakness as well. Keeping blood glucose levels in the target range can prevent or delay further damage.
  • Diabetic patients may experience impairment in the muscle endurance, regardless of neuropathy presence. On the contrary, explosive and maximal muscle strength is related to presence and severity of neuropathic complications in diabetic patients.[24]

Foot Complications

  • Although it can hurt, diabetic nerve damage can also lessen the ability to feel pain, heat, and cold. A foot injury may go unnoticed until the skin breaks down and becomes infected.
  • Nerve damage can also lead to changes in the shape of feet and toes. Ulcers occur most often on the ball of the foot or on the bottom of the big toe.
  • Neglecting foot ulcers can result in infections, which can eventually lead to limb loss.
  • Screening for peripheral vascular disease should be performed by checking the distal pulses.
    Test for sensation should be performed by using:
    • A Semmes-Weinstein 5.07 (10 g) monofilament at specific sites to detect loss of sensation in the foot.
Monofilament.jpg


    • Vibration using a 128-Hz tuning fork
Tuning fork-2.jpg


  • A study done on diabetic patients with foot ulcer showed that piRNA, a factor related to better wound healing, have been elevated in wounds of diabetic patients who received negative pressure wound treatment(NPWT).[25]
  • A meta-analysis done on 2020 suggested that Autologous platelet-rich plasma treatment for diabetic foot ulcer enhances complete wound healing and speeds up the healing process. This study reported that this method doesn't increase the rate of side effects.[26]

Gastroparesis

Gastroparesis is a disorder affecting people with both type 1 and type 2 diabetes, where the stomach takes too long to empty its contents. It happens when nerves to the stomach are damaged. The vagus nerve controls the movement of food through the digestive tract. If the vagus nerve is damaged, the muscles of the stomach and intestines do not function normally, and there is stasis of food. Gastroparesis can make diabetes worse by making it more difficult to manage blood glucose. When food that has been delayed in the stomach finally enters the small intestine and is absorbed, blood glucose levels rise. If food stays too long in the stomach, it can cause problems like bacterial overgrowth because the food has fermented. Also, the food can harden into solid masses called bezoars that may cause nausea, vomiting, and obstruction in the stomach. Bezoars can be dangerous if they block the passage of food into the small intestine.

Hypoglycemia, Hyperglycemia, and a High Risk for Diabetic Comas

The symptoms of hypoglycemia include:

  • Shakiness
  • Dizziness
  • Sweating
  • Hunger
  • Headache
  • Pale skin color
  • Sudden moodiness or behavior changes, such as crying for no apparent reason
  • Clumsy or jerky movements
  • Seizure
  • Difficulty paying attention, or confusion
  • Tingling sensations around the mouth

COVID-19 infection

Risk Factors

  • Some possible factors that lead to more severe COVID-19 in diabetic patient have been summarized in the table below:[34]
Confirmed factors hypothesized factors
1- Glycemic instability

2- Immune deficiency(specially T-cell response)

3- Related comorbidities, like obesity and cardiac and renal disease

1- Chronic inflammation (elevated interleukin-6)

2- Elevated plasmin

3- Reduced ACE2

4- Increased furin (involved in virus entry into cell)

Complications:

  • Optimal metabolic control reduce the chance of complications in concurrent diabetes mellitus and COVID-19 in outpatients.

Management Considerations:

Anti-diabetic medication

Relation to ACE2 expression

Advantage

Disadvantage

Metformin

None
  • Lower level of IL-6
  • Higher albumin level
  • Lower COVID-19 related death
  • Potential cardiovascular benefits


Pioglitazone

Increased ACE2 production in animal models
  • Reduction in proinflammatory cytokines
  • Lower chance of lung injury
  • Increased chance of SARS-CoV-2 infection due to ACE2 overexpression

Sulfonylurea

None
  • No specific advantage has been found in patients with COVID-19

Dipeptidyl peptidase-4 inhibitors

None
  • No specific disadvantage has been found in patients with COVID-19

Sodium-glucose-co-transporter 2 inhibitors

Increased ACE2 production by kidney in human studies

Glucagon-like peptide-1 receptor agonists

Liraglutide has been linked with elevated ACE2 production in lung and heart in animal models
  • Potential cardiovascular benefits

Insulin

Increased Renal ACE2 production in animal models
  • No specific disadvantage has been found in patients with COVID-19

Prognosis

References

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  2. Mogensen CE, Vestbo E, Poulsen PL, Christiansen C, Damsgaard EM, Eiskjaer H, Frøland A, Hansen KW, Nielsen S, Pedersen MM (1995). "Microalbuminuria and potential confounders. A review and some observations on variability of urinary albumin excretion". Diabetes Care. 18 (4): 572–81. PMID 7497874.
  3. Qaseem A, Hopkins RH, Sweet DE, Starkey M, Shekelle P (2013). "Screening, monitoring, and treatment of stage 1 to 3 chronic kidney disease: A clinical practice guideline from the American College of Physicians". Ann. Intern. Med. 159 (12): 835–47. doi:10.7326/0003-4819-159-12-201312170-00726. PMID 24145991.
  4. Colberg SR, Sigal RJ, Fernhall B, Regensteiner JG, Blissmer BJ, Rubin RR, Chasan-Taber L, Albright AL, Braun B (2010). "Exercise and type 2 diabetes: the American College of Sports Medicine and the American Diabetes Association: joint position statement". Diabetes Care. 33 (12): e147–67. doi:10.2337/dc10-9990. PMC 2992225. PMID 21115758.
  5. Scognamiglio R, Negut C, Ramondo A, Tiengo A, Avogaro A (2006). "Detection of coronary artery disease in asymptomatic patients with type 2 diabetes mellitus". J. Am. Coll. Cardiol. 47 (1): 65–71. doi:10.1016/j.jacc.2005.10.008. PMID 16386666.
  6. Haan, Mary N.; Mungas, Dan M.; Gonzalez, Hector M.; Ortiz, Teresa A.; Acharya, Ananth; Jagust, William J. (2003). "Prevalence of Dementia in Older Latinos: The Influence of Type 2 Diabetes Mellitus, Stroke and Genetic Factors". Journal of the American Geriatrics Society. 51 (2): 169–177. doi:10.1046/j.1532-5415.2003.51054.x. ISSN 0002-8614.
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  14. Zhang, Shiqi; Xu, Juan; Cui, Di; Jiang, Shujuan; Xu, Xin; Zhang, Yi; Zhu, Dongchun; Xia, Li; Yard, Benito; Wu, Yonggui; Zhang, Qiu (2020). "Genotype Distribution of CNDP1 Polymorphisms in the Healthy Chinese Han Population: Association with HbA1c and Fasting Blood Glucose". Journal of Diabetes Research. 2020: 1–7. doi:10.1155/2020/3838505. ISSN 2314-6745.
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  16. Duan, Suyan; Chen, Jiajia; Wu, Lin; Nie, Guangyan; Sun, Lianqin; Zhang, Chengning; Huang, Zhimin; Xing, Changying; Zhang, Bo; Yuan, Yanggang (2020). "Assessment of urinary NGAL for differential diagnosis and progression of diabetic kidney disease". Journal of Diabetes and its Complications: 107665. doi:10.1016/j.jdiacomp.2020.107665. ISSN 1056-8727.
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  20. Larroumet, Alice; Rigo, Marine; Lecocq, Maxime; Delyfer, Marie-Noelle; Korobelnik, Jean-François; Monlun, Marie; Foussard, Ninon; Poupon, Pauline; Blanco, Laurence; Mohammedi, Kamel; Rigalleau, Vincent (2020). "Previous dramatic reduction of HbA1c and retinopathy in Type 2 Diabetes". Journal of Diabetes and its Complications. 34 (7): 107604. doi:10.1016/j.jdiacomp.2020.107604. ISSN 1056-8727.
  21. Chung, Jin Ook; Park, Seon-Young; Chung, Dong Jin; Chung, Min Young (2020). "Serum myostatin levels are positively associated with diabetic retinopathy in individuals with type 2 diabetes mellitus". Journal of Diabetes and its Complications. 34 (7): 107592. doi:10.1016/j.jdiacomp.2020.107592. ISSN 1056-8727.
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  23. Zhang, Hui; Li, Tingting; Cai, Xuan; Wang, Xiangning; Li, Shiwei; Xu, Biwei; Wu, Qiang (2020). "MicroRNA-203a-3p regulates CoCl2-induced apoptosis in human retinal pigment epithelial cells by targeting suppressor of cytokine signaling 3". Journal of Diabetes and its Complications: 107668. doi:10.1016/j.jdiacomp.2020.107668. ISSN 1056-8727.
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  25. Kapusta, Przemysław; Konieczny, Paweł S.; Hohendorff, Jerzy; Borys, Sebastian; Totoń-Żurańska, Justyna; Kieć-Wilk, Beata M.; Wołkow, Paweł P.; Malecki, Maciej T. (2020). "Negative pressure wound therapy affects circulating plasma microRNAs in patients with diabetic foot ulceration". Diabetes Research and Clinical Practice. 165: 108251. doi:10.1016/j.diabres.2020.108251. ISSN 0168-8227.
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  27. Bornstein SR, Rubino F, Khunti K, Mingrone G, Hopkins D, Birkenfeld AL; et al. (2020). "Practical recommendations for the management of diabetes in patients with COVID-19". Lancet Diabetes Endocrinol. 8 (6): 546–550. doi:10.1016/S2213-8587(20)30152-2. PMC 7180013 Check |pmc= value (help). PMID 32334646 Check |pmid= value (help).
  28. Remuzzi A, Remuzzi G (2020). "COVID-19 and Italy: what next?". Lancet. 395 (10231): 1225–1228. doi:10.1016/S0140-6736(20)30627-9. PMC 7102589 Check |pmc= value (help). PMID 32178769 Check |pmid= value (help).
  29. Gupta, Ritesh; Hussain, Akhtar; Misra, Anoop (2020). "Diabetes and COVID-19: evidence, current status and unanswered research questions". European Journal of Clinical Nutrition. 74 (6): 864–870. doi:10.1038/s41430-020-0652-1. ISSN 0954-3007.
  30. Chen, Yuchen; Yang, Dong; Cheng, Biao; Chen, Jian; Peng, Anlin; Yang, Chen; Liu, Chong; Xiong, Mingrui; Deng, Aiping; Zhang, Yu; Zheng, Ling; Huang, Kun (2020). "Clinical Characteristics and Outcomes of Patients With Diabetes and COVID-19 in Association With Glucose-Lowering Medication". Diabetes Care. 43 (7): 1399–1407. doi:10.2337/dc20-0660. ISSN 0149-5992.
  31. Zhang Q, Wei Y, Chen M, Wan Q, Chen X (2020). "Clinical analysis of risk factors for severe COVID-19 patients with type 2 diabetes". J Diabetes Complications: 107666. doi:10.1016/j.jdiacomp.2020.107666. PMC 7323648 Check |pmc= value (help). PMID 32636061 Check |pmid= value (help).
  32. 32.0 32.1 Guo, Weina; Li, Mingyue; Dong, Yalan; Zhou, Haifeng; Zhang, Zili; Tian, Chunxia; Qin, Renjie; Wang, Haijun; Shen, Yin; Du, Keye; Zhao, Lei; Fan, Heng; Luo, Shanshan; Hu, Desheng (2020). "Diabetes is a risk factor for the progression and prognosis of COVID-19". Diabetes/Metabolism Research and Reviews: e3319. doi:10.1002/dmrr.3319. ISSN 1520-7552.
  33. 33.0 33.1 Gupta, Ritesh; Hussain, Akhtar; Misra, Anoop (2020). "Diabetes and COVID-19: evidence, current status and unanswered research questions". European Journal of Clinical Nutrition. 74 (6): 864–870. doi:10.1038/s41430-020-0652-1. ISSN 0954-3007.
  34. Gupta, Ritesh; Hussain, Akhtar; Misra, Anoop (2020). "Diabetes and COVID-19: evidence, current status and unanswered research questions". European Journal of Clinical Nutrition. 74 (6): 864–870. doi:10.1038/s41430-020-0652-1. ISSN 0954-3007.
  35. Bornstein SR, Rubino F, Khunti K, Mingrone G, Hopkins D, Birkenfeld AL; et al. (2020). "Practical recommendations for the management of diabetes in patients with COVID-19". Lancet Diabetes Endocrinol. 8 (6): 546–550. doi:10.1016/S2213-8587(20)30152-2. PMC 7180013 Check |pmc= value (help). PMID 32334646 Check |pmid= value (help).
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