Glycemic Impact on Knee Osteoarthritis Symptoms on Physical, Radiographic, and Inflammatory Markers among Individuals Aged 50 and Over with Diabetes

Summary

Here, we present a protocol to assess glycemic control using capillary blood glucose (CBG) and glycated hemoglobin A1C (HbA1C) levels. This study investigates the impact of hyperglycemia on knee osteoarthritis (KOA) symptoms, physical performance, physical activity level, radiographic severity, and inflammation in older adults with diabetes.

Abstract

This study explores hyperglycemia's influence on knee osteoarthritis (KOA) related symptoms, physical performance, physical activity level, radiographic severity, and inflammation in older adults. Prolonged hyperglycemic states contribute to advanced glycation end-product (AGE) formation, which worsens KOA symptoms. Capillary blood glucose (CBG) and glycated hemoglobin A1C (HbA1C) levels are commonly used in laboratory tests for glycemic assessment, offering distinct advantages and limitations. Participants were divided into good and poor glycemic control groups based on their CBG and HbA1C levels. KOA clinical severity and physical activity were measured using the knee injury and osteoarthritis outcome score (KOOS) and international physical activity questionnaire. Physical performance was measured with hand grip strength, gait speed, time-up-and-go (TUG), and 5 times sit-to-stand (5STST). Knee X-rays were performed, and serum enzyme-linked immunosorbent assay (ELISA) analysis was conducted for IL-1β, IL-4, CRP, NF-κB, and AGE. Three hundred recruited participants (mean age [SD] = 66.40 years (5.938) with CBG, of fasting blood sugar > 7.0 mmol/L and random blood sugar > 11.1 mmol/L, (N = 254) were compared with KOOS pain (p=0.008) and symptoms (p=0.017) and 5STST (p=0.015); while HbA1c > 6.3% (N = 93) was compared with 5STST (p=0.002), and AGEs (p=0.022) based on Mann Whitney U test. Logistic regression revealed significant associations between glycemic control and lower limb muscle strength, radiological severity, laboratory markers, and between glycemic status and KOOS pain and symptoms. However, these associations did not remain significant after adjusting for BMI. Poor glycemic status alone was associated with better function in sport and recreation domains after antidiabetic medication adjustment, suggesting anti-inflammatory and analgesic effects that masked the effect of high blood sugar. Future studies could explore the predictive ability of glycemic assessment for poor knee function and physical performance while accounting for the effects of the medication.

Introduction

Knee osteoarthritis (KOA) increases in prevalence with age, with the knee being a major weight-bearing joint¹. KOA usually manifests with stiffness and chronic pain at the knee joint, which limits mobility, reduces quality of life, and increases the risk of cardiovascular disease². Diabetes mellitus, which is also related to age, contributes to the risk of KOA development, as elevated glucose and lipids levels promote advanced glycation end product (AGE) formation, leading to chronic joint inflammation and cartilage degeneration³. Despite the availability of healthcare services, two in five Malays....

Protocol

The study protocol was in compliance with the Declaration of Helsinki and was approved by the Universiti Kebangsaan Malaysia Ethics Committee (reference number: JEP-2022-001).

1. Participant recruitment

1. Through convenience sampling, select the study population from community-dwelling adults with KOA aged 50 years and above in Kuala Lumpur and Selangor. Recruited participants from senior citizens' organizations and diabetes and orthopedic clinics.
   NOTE: The presence of KOA is defined with self-reported physician-diagnosed KOA or those in fulfillment of the American College of Rheumatology (ACR) clinica....

Discussion

Venous blood collection is often preferred for laboratory tests over capillary blood sampling in terms of accuracy of results²⁹. The HbA1c is strongly associated with diabetes complications, stable chemical nature and well-standardized laboratory tests. As the HbA1c reflects glycemic control over 3 months it does not require fasting samples, while one-time capillary blood sampling could reflect one-point glycemic status, which is influenced by the timing and the contents of recent meals. Both glyc.......

Materials

Name	Company	Catalog Number	Comments
Butterfly needle	BD Vacutainer	367282
G*Power 3.1	Heinrich-Heine-University	https://www.psychologie.hhu.de/arbeitsgruppen/allgemeine-psychologie-und-arbeitspsychologie/gpower	Heinrich-Heine-University, Düsseldorf
Glucometer and test strips	Contour plus	https://www.diabetes.ascensia.my/en/products/contour-plus/	Basel, Switzerland
Human CRP(C-Reactive Protein) ELISA Kit	Elabscience	E-EL-H0043-96T	ELISA kit
Human IL-1β(Interleukin 1 Beta) ELISA Kit	Elabscience	E-EL-H0149-96T	ELISA kit
Human IL-4(Interleukin 4) ELISA Kit	Elabscience	E-EL-H0101-96T	ELISA kit
Human NF-κB-p105 subunit	Bioassay Technology Laboratory	E0003Hu	ELISA kit
Human NF-κBp105(Nuclear factor NF-kappa-B p105 subunit)	Elabscience	E-EL-H1386-96T	ELISA kit
Manual hand dynamometer	Jamar	5030J1	Warrenville, Illinois, USA
Portable Body Composition Analyzer	InBody ASIA	https://inbodyasia.com/products/inbody-270/	Inbody 270, Cheonan, Chungcheongnam-do
Portable stadiometer	Seca	213 1821 009	SECA 213, Hamburg, Germany