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

Introduction:

Diabetes is a group of diseases that leads to high glucose levels in the blood, mainly when the pancreas is not able to produce enough insulin, or when the body is not able to utilize the insulin it produces. High blood sugar levels are a hallmark of diabetes (diabetes mellitus), caused by inadequate insulin production in the pancreas, and the most important predictor of people who have diabetes developing chronic kidney disease (CKD).

Diabetes is mainly of two types: type 1 (juvenile diabetes) and type 2 (adult-onset diabetes). Type 2 diabetes (non-insulin-dependent diabetes) affects more people than type 1 diabetes (insulin-dependent diabetes), which accounts for roughly 90 to 95 percent of cases (mostly adults) of diabetes. Most people over 40 have type 2 diabetes, and although among younger generations, particularly kids and teenagers, it is becoming increasingly common. However, type 1 diabetes typically appears in children or adolescents.

What Are the Symptoms Indicating Diabetes Developing in Chronic Kidney Disease?

• Protein in the urine.

• Hypertension.

• Leg pain.

• Swelling.

• Increased urination (especially at night).

• Abnormal blood tests (glomerular filtration rate GFR).

• Nausea and vomiting.

• Weakness.

• Pallor.

• Anemia (lack of enough healthy red blood cells in the blood).

• Itching.

• Diabetic eye disease (or diabetic retinopathy - a complication of diabetes that affects a person’s eyes).

What Are the CKD Risk Factors That Need to Be Managed?

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

2. Treating diabetic people with blood pressure-lowering medications may stop or delay the onset of CKD. These drugs lower blood pressure and lessen urine protein, a significant risk for renal (kidney) disease.

3. As risk factors for heart disease and stroke (interrupted blood supply to the brain), controlling blood sugar, blood pressure, and cholesterol levels is 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?

The glycemic control range mainly focuses on maintaining blood glucose levels in the desirable range to prevent both hyperglycemia and hypoglycemia.

• The glucose target for achieving HBA1c is seven percent. Thus, 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 seven 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 seven percent rather than the target HBA1c of seven percent endorsed in the 2007 guidelines.

• It is also advised to customize the HbA1c objectives for each individual because lower A1c levels are linked to a higher risk of hypoglycemia, leading to myocardial infarction, seizures, stroke, or death in the elderly and fragile, in people with irregular eating habits, those on insulin and sulfonylureas, and people with chronic kidney disease.

What Are Medicinal Interventions Utilized to Treat Diabetic Nephropathy?

Diabetic nephropathy (diabetic kidney disease) refers to the loss of kidney functions due to diabetes. The condition is one of the primary causes of chronic kidney disease and should be managed effectively.

Diabetes treatment is always evolving as new medicines are made available for usage, and the latest information about the safety profiles of drugs is also made accessible. Modifications in diabetes drug dosage used in chronic kidney disease are as follows:

1. Insulin

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 five to 15 minutes, peak after 30 to 90 minutes, and last for an average of five hours. According to certain research, Glulisine's action duration is slightly longer than that of 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 or multiple daily injections).

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 (watery or loose stool), bloating (a feeling of fullness or tightness in the stomach), and cramps are the most typical adverse effects. Long-term use has been linked to vitamin B12 insufficiency.

Metformin should be used as suggested:

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

• If the estimated glomerular filtration rate (eGFR) is between 45 and 59 milliliters per minute (mL/min), Metformin dosage should be used cautiously and closely monitor renal function (every three to six months).

• If eGFR is between 30 to 44 mL/min,the maximum dose of 1000 milligrams/day of Metformin or 50 percent dose reduction is recommended. Also, every three months, one should check on the kidney function. The new therapy should not be started.

• If eGFR is 30 mL/min, Metformin should be avoided.

B. Sulfonylureas

These stimulate insulin production by binding to the sulfonylurea receptor on the pancreatic beta-cells. They can result in hypoglycemia and often reduce HbA1c (hemoglobin A1c) by 1.5 to two percent. First-generation sulfonylureas are rarely administered, and second-generation sulfonylureas are frequently used. The renal clearance of sulfonylureas and their metabolites increases the risk of hypoglycemia when the GFR decreases.

First-Generation Sulfonylureas:

• Acetohexamide - Prevent use.

• Chlorpropamide - If eGFR is 50 to 80 mL/min, reduce the dose by 50 percent.

• Tolazamide - Prevent use.

• Tolbutamide - Prevent use.

Second-Generation Sulfonylureas:

• Glipizide - eGFR less than 30 mL/min; use with caution.

• Glimepiride - eGFR less than 60 mL/min; use with caution.

• Glyburide - Prevent the use.

• Gliclazide - No dose adjustment (controversial).

4. Alpha-Glucosidase Inhibitor

They 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 HbA1c by 0.5 to 0.8 percent. These include:

• Miglitol - eGFR 25 mL/min or serum creatinine (Cr) more than two milligrams/decilitre: Prevent use.

• Acarbose - Serum Cr more than two milligrams/decilitre: Prevent use.

5. Dipeptidyl Peptidase-4 Inhibitors

They prevent the breakdown of incretin hormones like glucose-like peptides (GLP-1). This family of drugs lowers HbA1c by 0.5 to 0.8 percent without affecting weight. These include:

• Sitagliptin - eGFR more than or equal to 50 mL/min: 100 milligrams per day,

  • eGFR 30 to 49 mL/min: 50 milligrams per day,

  • eGFR 30 mL/min: 25 milligrams per day.

• Saxagliptin - eGFR more than 50 mL/min: 2.5 or five milligrams daily.

• Linagliptin - No dosage modification.

• Analogliptin - eGFR more than 60 mL/min: 25 milligrams daily

  • eGFR 30 to 59 mL/min:12.5 milligrams daily.

  • eGFR 30 mL/min: 6.25 milligrams daily.

6. Sodium-Glucose Co-transporter 2 (SGLT2) Inhibitors

SGLT2 inhibitors decrease glucose absorption from the kidney, increasing glucose excretion and lowering HbA1c by 0.9 to 1.0 percent. Up to five kilograms of weight loss in one year is feasible because of the rise in urine glucose. These include:

• Canagliflozin - eGFR 45 to less than 60 mL/min: maximum dose 100 milligrams once daily. eGFR less than 45 mL/min, prevent use.

• Dapagliflozin - eGFR less than 60 mL/min, prevent use.

• Empagliflozin - eGFR less than 45 mL/min, prevent use.

What Is the Treatment for Diabetic Patients on Dialysis With Recent Organ Transplant?

Diabetic patient on dialysis and recent organ transplant is managed and treated in the following ways:

• Some of the 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. Therefore, continuous glucose monitoring should be done for patients undergoing hemodialysis along with individualized insulin regimens to prevent both hyper- and hypoglycemia pre- and post-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 such patients. However, during overnight peritoneal dialysis with a cycler, an increased glucose load with a fixed mixture insulin combination, such as 70/30 or 75/25 insulins, is administered at the beginning of peritoneal dialysis.

• Due to the requirement for more or less fluid drainage, the glucose concentration of the dialysate is frequently modified for peritoneal dialysis by the nephrologist, and insulin adjustment is done after consulting the endocrinologist.

• Glycemic control may drastically deteriorate in the early post-transplant interval. This is because anti-rejection treatments, such as glucocorticoids, calcineurin inhibitors, and sirolimus, are introduced, and insulin resistance increases.

• 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 considered while managing patients with diabetes and nephropathy (loss of kidney function). 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.