Management of Diabetes in Patients With Progressive Chronic Kidney Disease - An Overview

Introduction:

High blood sugar levels are a hallmark of diabetes, caused by inadequate insulin production or flaws in how the hormone functions in the body. Type 2 diabetes affects more people than type 1 diabetes (insulin-dependent diabetes), which only accounts for roughly 90 to 95 percent of cases of diabetes. Type 2 diabetes is also known as noninsulin-dependent diabetes. Most people over 40 have type 2 diabetes, and although it is among younger generations, particularly kids and teenagers, it is becoming increasingly common.

Diabetes damages small blood vessels throughout the body, including the retina, kidneys, and other organs and tissues such as the skin, nerves, muscles, intestines, and heart. Diabetes can cause high blood pressure and rapid artery hardening, leading to heart disease and vision problems.

According to research, high blood pressure is the most important predictor of people who have diabetes developing chronic kidney disease. Specific high blood pressure medications, such as ACE inhibitors and Angiotensin-2 receptor blockers (ARBs), might be the most efficient in preventing diabetic kidney disease. People with diabetes must maintain their blood pressure below 130/80.

What Symptoms Indicate That a Diabetic Is Developing Chronic Kidney Disease (CKD)?

1. Protein in the urine.

2. Hypertension.

3. Leg pain.

4. Swelling.

5. Increased urination (especially at night).

6. Abnormal blood tests (glomerular filtration rate GFR).

7. Nausea and vomiting.

8. Weakness.

9. Pallor.

10. Anemia.

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11. Itching.

12. Diabetic eye disease.

What Are CKD Risk Factors to Be Managed?

1. Controlling blood sugar and blood pressure has been found to reduce the risk of developing kidney disease in patients with diabetes and high blood pressure.

2. Studies have suggested that treating diabetic individuals with blood pressure-lowering medications may help to stop or delay the onset of diabetic kidney damage. These drugs lower blood pressure and lessen urine protein, which is a significant risk for renal disease.

3. As risk factors for heart disease and stroke, controlling blood sugar, blood pressure, and cholesterol levels are crucial.

4. Early kidney disease detection and treatment is crucial for persons with diabetes to help prevent or postpone renal disease because it raises the risk of developing heart disease and

stroke.

What Is the Glycemic Control Range?

Glucose target of achieving HBA1c - 7.0 percent. To postpone or prevent nephropathy, glycemic management is crucial. The ADA(American Diabetes Association) has typically advised a goal HBA1c of less than or around 7 percent for managing diabetes. The ADA recommends stricter (6.5 percent) or higher (8 percent) HBA1c objectives for specific populations. AACE(American Association of Clinical Endocrinology) advises setting a target HBA1c of less than 6.5 percent in healthy individuals at low risk for hypoglycemia. Still, it also recognizes that individual targets must be set. The updated 2012 Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines for Diabetes and CKD(chronic kidney disease) indicate an HBA1c of 7.0 percent rather than the target HBA1c of 7.0 percent endorsed in the 2007 guidelines.

A1c objectives should be customized for each individual because lower A1c levels are linked to a higher risk of hypoglycemia. The chances of hypoglycemia, which can lead to harm, myocardial infarction, seizures, stroke, or death, are greatest in the elderly and fragile, in people with irregular eating habits, those on insulin and sulfonylureas, and people with chronic kidney disease. For those with reduced lifespans, a history of known hypoglycemia or hypoglycemia that is uninformed, chronic kidney disease, and children, higher A1c objectives should be considered.

What Are Medicinal Interventions Utilized to Treat Diabetic Nephropathy?

Medical treatment for diabetes is always evolving as new treatments are made available for usage and as new information about the safety profiles of drugs is made accessible. For modifications in dosage for diabetes drugs used in chronic kidney disease-

1. Insulin

Patients with advanced kidney disease are more likely to have hypoglycemia because they clear insulin and some diabetic medicines less efficiently, have lower kidney mass, and impaired renal gluconeogenesis. Between 30 and 80 percent of insulin is removed by the kidney; decreased renal function is linked to a lengthened insulin half-life and a reduction in insulin needs as the glomerular filtration rate drops. Patients with chronic kidney disease can use any insulin formulation on the market, and there is no recommended dosage reduction for those taking insulin. To reach desired glycemic levels while preventing hypoglycemia, The insulin dosage, kind, and route of administration must be customized for each patient.

Patients with chronic kidney disease can use any insulin formulation on the market, and there is no recommended dosage reduction for those taking insulin. To reach desired glycemic levels while preventing hypoglycemia, The insulin dosage, kind, and route of administration must be customized for each patient.

2. Rapid-acting Insulin

The quickest absorbed and best for immediate blood sugar correction or prandial insulin demands, the rapid-acting insulin analogs named Aspart, Lispro, and Glulisine most closely match physiologic insulin production. They start to work after 5 to 15 minutes, peak after 30 to 90 minutes and last for an average of 5 hours. According to certain research, Glulisine's action duration is slightly longer than the other two rapid-acting insulins. These insulins can be administered up to 15 minutes before a meal. Using an insulin pump to administer continuous subcutaneous insulin and Several daily injections are used in "basal-bolus treatment," or BBT (MDI).

Rapid-acting insulin may help synchronize the postprandial blood glucose peak that coincides with the insulin peak in patients with diabetes, Stage 4-5 chronic kidney disease, and those on dialysis since they frequently have delayed stomach emptying. Postprandial rapid-acting insulin dose might be worth a shot in individuals with nausea who are unsure how much they will eat. Postprandial dosage may also benefit peritoneal dialysis patients because they often consume fewer calories than they might anticipate while receiving substantial quantities of calories through their dialysis fluid.

3. Oral Medications

A. Metformin

In addition to improving insulin sensitivity and reducing hepatic gluconeogenesis, metformin does not result in hypoglycemia and, in some patients, may produce weight reduction. Diarrhea, bloating, and cramps are the most typical adverse effects. Long-term use has been linked to vitamin B12 insufficiency.

• Per FDA (Food and Drug Administration), do not use if serum creatinine is more than 1.5 mg/dl in men and more than 1.4 milligrams/decilitre in women.

• eGFR 45-59: Use caution with dosage and closely monitor renal function (every 3–6 months)

• eGFR 30-44: The maximum dose of 1000 milligrams/day or 50 percent dose reduction. Every three months, check on your kidney function. Do not begin as a new therapy.

• eGFR 30: Avoid using

B. Sulfonylureas

Stimulate the production of Insulin via binding to the Sulfonylurea receptor on the pancreatic beta-cells. They can result in hypoglycemia and often reduce A1c by 1.5–2 percent. Rarely are first-generation sulfonylureas administered. Second-generation sulfonylureas, such as Glipizide, Glimepiride, Glyburide, and Gliclazide, are frequently used. The sulfonylureas will reduce A1c by 1 percent to 2 percent. The renal clearance of Sulfonylureas and their metabolites increases the risk of hypoglycemia when Glomerular Filtration Rate decreases.

First-generation Sulfonylureas:

• Acetohexamide - Prevent use.

• Chlorpropamide - eGFR (estimated Glomerular Filtration Rate) - 50-80: reduce dose by 50 percent.

• Tolazamide - Prevent use.

• Tolbutamide - Prevent use.

Second-generation Sulfonylureas:

• Glipizide - eGFR less than 30, use with caution.

• Glimepiride - eGFR less than 60, use with caution.

• Glyburide - Prevent the use.

• Gliclazide - No dose adjustment (controversial).

3. Alpha-glucosidase inhibitor

Acarbose and Miglitol, Alpha-glucosidase inhibitors slow down the breakdown of oligo- and disaccharides in the small intestine, decreasing glucose absorption after a meal. The main adverse reactions are bloating, flatulence, and abdominal cramping. They often do not cause weight gain or loss and reduce A1c by 0.5-0.8 percent.

• Miglitol - eGFR 25 or serum Cr more than 2 milligrams/decilitre: Prevent use.

• Acarbose - serum Cr more than 2 milligrams/decilitre: Prevent use.

4. Dipeptidyl peptidase-4 inhibitors

Dipeptidyl peptidase 4 (DPP 4) inhibitors, such as Sitagliptin, Saxagliptin, Linagliptin, and Alogliptin, prevent the breakdown of incretin hormones like GLP-1. This family of drugs lowers A1c by 0.5-0.8 percent without affecting weight.

A) Sitagliptin - eGFR more than or equal to50: 100 milligrams per day,

• eGFR 30-49: 50 milligrams per day,
• eGFR 30: 25 milligrams per day.

B) Saxagliptin- eGFR more than 50: 2.5 or 5 milligrams daily.

C) Linagliptin - No dosage modification.

D) Analogliptin - eGFR more than 60: 25 milligrams daily

• eGFR 30-59:12.5 milligrams daily.
• eGFR 30:6.25 milligrams daily.

5. Sodium-glucose co-transporter 2 (SGLT2) inhibitors

SGLT2 inhibitors decrease glucose absorption from the kidney, increasing glucose excretion and lowering A1c by 0.9–1.0 percent. Up to 5killograms of weight loss in one year is feasible because of the rise in urine glucose.

A) Canagliflozin - eGFR 45 to less than 60: maximum dose 100 milligrams once daily.

• eGFR less than 45, prevent use.

B) Dapagliflozin - eGFR less than 60, prevent use.C) Empagliflozin -eGFR less than 45, prevent use.

What Are the Treatments Provided to Diabetic Patients on Dialysis and Those Who Have Recently Undergone Organ Transplants?

A few oral medications can be administered safely in dialysis patients, especially if the diabetes is mild. The majority of people, however, will require insulin for blood sugar control.

The timing of dialysis may impact the insulin clearance rates of patients receiving hemodialysis. After conducting continuous glucose monitoring on patients undergoing hemodialysis, it was found that patients' glycemic reactions during hemodialysis are unique, necessitating the individualization of their insulin regimens to prevent both hyper- and hypoglycemia during and after hemodialysis. Patients receiving peritoneal dialysis are exposed to high glucose levels in the dialysate, which can cause uncontrolled hyperglycemia. A typical basal/bolus insulin regimen works best for patients receiving peritoneal dialysis continuously. However, when performing overnight peritoneal dialysis with a cycler, it may be appropriate to cover the increased glucose load with a fixed mixture insulin combination, such as 70/30 or 75/25 insulins, administered at the beginning of peritoneal dialysis. Due to the requirement for more or less fluid drainage, the nephrologist prescribing peritoneal dialysis frequently modifies the glucose concentration of the dialysate. Such modifications must be discussed with the endocrinologist for the insulin dosages to be adjusted appropriately.

Glycemic control may drastically deteriorate in the early post-transplant interval. This is because anti-rejection treatments such as Glucocorticoids, Calcineurin inhibitors, and Sirolimus have been introduced, and insulin resistance has increased. Patients may also suffer other changes in their daily routines, such as modifications to their food, level of activity, and medicine. Glycemic control might vary significantly due to numerous factors, necessitating constant monitoring of blood glucose levels and prescription modifications.

Conclusion:

Multiple aspects of care must be taken into consideration while managing patients with diabetes and nephropathy. Significantly, glycemic management should be adjusted for the patient, achieving the required control to reduce problems but done in a supervised manner. The diabetic regimen should be adjusted if microalbuminuria or decreases in glomerular filtration rate are seen during routine screening for the development of nephropathy. Diabetologists, nephrologists, dietitians, diabetes educators, and other professionals with experience in the complications of diabetes are required to provide a multimodal care program to slow disease progression in the prevention and treatment of diabetic nephropathy and its complications.

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