Diabetes and Microvascular Complications

[madman]

Diabetes-Related Microvascular Complications – A Practical Approach (2022)
Basem M. Mishriky, MD, Doyle M. Cummings, Pharm, FCP, FCCP, James R. Powell, MD


DIABETIC SYMMETRIC POLYNEUROPATHY

What is Diabetic Symmetric Polyneuropathy?

Diabetic neuropathy is classified into diffuse neuropathy, mononeuropathy, and radiculopathy/polyradiculopathy.1 Diabetic symmetric polyneuropathy (DSPN) is the most common form of diffuse neuropathy, which is the most common form of diabetic neuropathy.1 DSPN affects 50% of individuals with type 2 diabetes (T2DM) after 10 years of disease duration and at least 20% of individuals with type 1 diabetes (T1DM) after 20 years of diagnosis.1 DSPN can be referred to as distal symmetric polyneuropathy or even, although less accurate, as diabetic neuropathy.2

The American Academy of Neurology, the American Association of Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation define distal symmetric polyneuropathy (including DSPN) as polyneuropathy that must begin in the feet and include symptoms and signs that are the same on both sides of the body.3,4 The symptoms may be primarily sensory, primarily motor, or combined. The signs may include pain, impairment to touch, impairment to proprioception, weakness, and atrophy of muscles, depressed/absent ankle reflexes, or autonomic system.3,4 Signs are better predictors of polyneuropathy compared with symptoms and multiple concurrent abnormalities provide greater sensitivity in predicting polyneuropathy.

In the position statement by the American Diabetes Association (ADA), DSPN is defined as the presence of symptoms or signs of peripheral nerve dysfunctions after excluding other causes.1




*Can Patients without Numbness, Tingling, or Pain in the Feet have Diabetic Symmetric Polyneuropathy, and Why is this Important?

*How do Individuals with Diabetic Symmetric Polyneuropathy Present?
-Small-fiber involvement
-Large-fiber involvement

*Is Ongoing Foot Pain and Numbness in Individuals with Diabetes Always Diabetic Symmetric Polyneuropathy?

*What are the Criteria for Requesting a Nerve Conduction Study (Possible Reasons for Specialist Referral)?

*What are the Minimum Criteria Required to Diagnose Diabetic Symmetric Polyneuropathy?

*When Should the Health Care Providers Screen for Diabetic Symmetric Polyneuropathy?

*How Should the Health Care Providers Screen for Diabetic Symmetric Polyneuropathy?
-History
-Examination

*A Monofilament Test is Insensate to 5.07 but Intact to 6.65. Tuning Fork Vibrations Sense was Lost after Five Seconds. The Ankle Reflex and Pinprick Sensation were Intact Bilaterally. What is the Significance of that Foot Examination?

*What Measures can Health Care Providers do to Prevent Diabetic Symmetric Polyneuropathy and Ulcerations?
-Foot care education
-Proper footwear
-Glycemic control

*Management of Symptomatic Diabetic Symmetric Polyneuropathy




DIABETIC KIDNEY DISEASE

What is Diabetic Kidney Disease?

The ADA defined diabetic kidney disease (DKD) as chronic kidney disease (CKD) attributed to diabetes, and CKD as the persistent presence of elevated urinary albumin excretion low estimated glomerular filtration rate (GFR), or other manifestations of kidney damage.17

The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines defined CKD as abnormalities of the kidney structure or function present for ≥ 3 months.18 In 2007, the KDIGO guidelines recommended using the term “DKD” instead of “diabetic nephropathy” as there is no consensus definition of diabetic nephropathy.19 In 2020, the KDIGO guidelines used the term “Diabetes and CKD” over “DKD” although DKD was still considered appropriate, to ensure that other causes of CKD are considered and to avoid the assumption that all cases of CKD are caused by traditional diabetes pathophysiology.18




*How Common is Diabetic Kidney Disease?

*When should Health Care Providers Initiate Screening for Diabetic Kidney Disease? How Often Should the Screening be Done?

*How Should the Health Care Providers Interpret the Urine Albumin-to-creatinine Ratio?

*What is the Likelihood of Diabetic Kidney Disease in Individuals with Moderate/Severe Albuminuria?

*When to Refer to Nephrology?

*How Should the Health Care Providers Monitor Glycemic Control in Individuals with Diabetic Kidney Disease?

-What Measures can Reduce the Risk of Developing Diabetic Kidney Disease?
-Nutrition
-Lipid management
-Blood pressure
-Glycemic control
-Smoking

*A 55-year-old Individual with T2DM Treated with Metformin. His Last Creatinine was 1.7 mg/dL, GFR 51 mL/min/1.73 m2 , and UACR 389 mg/g. Should Metformin be Discontinued?

*How can Health Care Providers Delay Progression of Diabetic Kidney Disease? Renin–angiotensin system blockade
-Renin–angiotensin system blockade
-Sodium-glucose co-transporter-2 inhibitors

*What Anti-diabetic Medications Should be Added if Glycemic Control is not Achieved by Metformin and Sodium-glucose Co-transporter-2 Inhibitors?

*Novel Therapy in Diabetic Kidney Disease




DIABETIC RETINOPATHY

What is Diabetic Retinopathy?

The most common diabetes-related eye disease is diabetic retinopathy (DR). DR is characterized by a gradually progressive alteration in the retinal microvasculature resulting in areas of retinal nonperfusion with a resultant increase in vascular endothelial growth factor-A (VEGF). Elevated levels of VEGF can result in abnormal development of new blood vessels (neovascularization). Those new vessels can be friable and bleed into the vitreous cavity, causing vitreous hemorrhage. Vision-threatening DR develops in about 10% of people with diabetes and remains the leading cause of new cases of legal blindness.26




*When Should Screening Begin and How Frequently Should Testing be Done?

*Are Pregnant Women Screened Similarly?

*How Should the Health Care Providers Classify Diabetic Retinopathy?

*What is the Role of the Health Care Providers in Preventing/Treating Diabetic Retinopathy?
-Ensure regular eye examination
-Hyperglycemia
-Lipid control
-Lifestyle modifications

*What are the Treatment Options for Diabetic Retinopathy?




SUMMARY

In summary, microvascular complications including DSPN, DKD, and DR are common in patients with long-standing type 1 diabetes and new or existing type 2 diabetes and require active screening. Complications can be prevented or delayed by careful attention to risk factors, careful education and monitoring by the patient, and prompt evaluation and treatment by consultants when indicated. This evaluation, monitoring, prevention, and treatment can help improve patients’ quality of life and can be associated with reductions or delays in treatments such as dialysis with reduced cost.

 

[madman]

Fig. 1. A simplified view of the peripheral nervous system. (From Brownlee M, Aiello LP, Cooper ME, Vinik AI, Plutzky J, and Boulton AJM. Chapter 33: Complications of diabetes mellitus. In: Kronenberg HM, Larsen PR, Melmed S, and Polonsky KS, eds. Williams Textbook of Endocrinology. 13th ed. Elsevier: 2016: 1484-1581; with permission.)

 

[madman]

Fig. 2. Frequency of monitoring renal functions in DKD. The numbers in the boxes are a guide to the frequency of visits (number of times/year). (From Chapter 2: Definition, identification, and prediction of CKD progression. Kidney Int Suppl (2011). 2013; 3(1): 63-72; with permission.)

 

[madman]

Fig. 3. Features of mild and moderate to severe stages of NPDR. (A) Fundus photograph showing mild NPDR with microaneurysms. (B) Fundus photograph showing moderate NPDR with hemorrhages, hard exudates, and microaneurysms. (C) Fundus photograph showing moderate NPDR with mild DME. (D) Fundus photograph showing moderate macular edema. (E) Fluorescein angiogram showing moderate NPDR with non–center-involving DME. (F) Fundus photograph showing severe NPDR with center-involving DME. (From Wong TY, Sun J, Kawasaki R, Ruamviboonsuk P, Gupta N, Lansingh VC, Maia M, Mathenge W, Moreker S, Muqit MMK, Resnikoff S, Verdaguer J, Zhao P, Ferris F, Aiello LP, Taylor HR. Guidelines on Diabetic Eye Care: The International Council of Ophthalmology Recommendations for Screening, Follow-up, Referral, and Treatment Based on Resource Settings. Ophthalmology. 2018 Oct; 125(10): 1608-1622; with permission.)

 

[madman]

KEY POINTS

*Screen for microvascular complications at the time of diagnosis of type 2 diabetes

*Inspection of the feet is encouraged at every visit

*Renal evaluation should be performed at least annually to screen for diabetic kidney disease

*Retinal evaluation by an expert should be performed regularly

 

[madman]

CLINICAL CARE POINTS

*Screening for diabetes-related microvascular complications should start immediately at the time of diagnosis of T2DM and within 5 years after the diagnosis of T1DM


DSPN:

*Screening for DSPN is essential as around 50% of individuals with DSPN are asymptomatic and will not volunteer symptoms

*Before diagnosing DSPN, HCP may need to rule out other causes of neuropathy

*In clinical practice, nerve conduction studies and skin biopsy are rarely indicated

*In individuals with DSPN, an annual foot examination may not be adequate and an exam/ inspection at every visit is suggested

*Patients should be encouraged to check their feet daily

*Foot care education should be provided to the patient at least at the initial visit and as indicated

*In individuals who are at high risk for ulceration and amputations, HCP should prescribe diabetic shoes and consider a podiatry referral



DKD:

*In individuals without DKD, annual serum creatinine and UACR are required

*An abnormal UACR requires 2 to 3 abnormal specimens within a 3- to 6-month period to confirm the diagnosis of albuminuria

*If the GFR is < 30 mL/min/1.73 m2, there is a rapid worsening of renal functions, or the etiology is unclear, the patient should be referred to nephrology

*The reliability of hemoglobin A1c is low in advanced DKD

*In individuals with DKD, RAS blockade agent and/or SGLT-2i are recommended. Finerenone can reduce CKD progression and cardiovascular events


DR:

*An eye examination by an expert is needed at least annually for the first 2 years

*Individuals with diagnosed DR may require a more frequent monitoring schedule

*Digital retinal photography with remote reading may be an option in locations with limited access to ophthalmologic evaluation

*In patients seeking pregnancy, a comprehensive eye examination within 1 year before conception and then during pregnancy is indicated as pregnancy may exacerbate DR

*The use of RAS inhibitor has shown to reduce the incidence and risk of progression of DR

 

[ZaneBuckley]

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