The Relationship between BMI and Glycated Albumin to Glycated Hemoglobin (GA/A1c) Ratio According to Glucose Tolerance Status

<div><p>Glycated albumin to glycated hemoglobin (GA/A1c) ratio is known to be inversely related with body mass index (BMI) and insulin secretory capacity. However, the reasons for this association remain unknown. We aimed to investigate whether BMI directly or indirectly influences GA/A1c by exerting effects on insulin secretion or resistance and to confirm whether these associations differ according to glucose tolerance status. We analyzed a total of 807 subjects [242 drug-naïve type 2 diabetes (T2D), 378 prediabetes, and 187 normal glucose tolerance (NGT)]. To assess the direct and indirect effects of BMI on GA/A1c ratio, structural equation modeling (SEM) was performed. GA/A1c ratio was set as a dependent variable, BMI was used as the independent variable, and homeostasis model assessment-pancreatic beta-cell function (HOMA-β), homeostasis model assessment-insulin resistance (HOMA-IR), glucose level were used as mediator variables. The estimates of a direct effect of BMI on GA/A1c to be the strongest in NGT and weakest in T2D (−0.375 in NGT, −0.244 in prediabetes, and −0.189 in T2D). Conversely, the indirect effect of BMI on GA/A1c exerted through HOMA-β and HOMA-IR was not statistically significant in NGT group, but significant in prediabetes and T2D groups (0.089 in prediabetes, −0.003 in T2D). It was found that HOMA-β or HOMA-IR indirectly influences GA/A1c in T2D and prediabetes group through affecting fasting and postprandial glucose level. The relationship between GA/A1c and BMI is due to the direct effect of BMI on GA/A1c in NGT group, while in T2D and prediabetes groups, this association is mostly a result of BMI influencing blood glucose through insulin resistance or secretion.</p></div

Structural equation models for the GA/A1c ratio in NGT (A), prediabetes (B) and diabetes group (C).

<p>*<i>P</i><0.05; **<i>P</i><0.01;*** <i>P</i><0.001.</p

Structural equation models for the GA/A1c ratio.

<p>Structural equation models for the GA/A1c ratio.</p

Baseline characteristics.

<p>Data presented as n (%) or mean ± standard deviation.</p>†<p>: The difference between NGT and Prediabetes : p<0.05 after Bonferroni correction.</p>‡<p>: The difference between NGT and Diabetes : p<0.05 after Bonferroni correction.</p>#<p>: The difference between Prediabetes and Diabetes : p<0.05 after Bonferroni correction.</p><p>Abbreviations: NGT, normal glucose tolerance; BMI, body mass index; WHR, waist-to-hip ratio; SBP, systolic blood pressure; DBP, diastolic blood pressure; HbA1c, glycated hemoglobin; GA, glycated albumin; GA/A1c, ratio of glycated albumin to glycated hemoglobin; HOMA-β, homeostasis model assessment- pancreatic beta-cell function; HOMA-IR, homeostatsis model assessment-insulin resistance; LDL, low-density lipoprotein; HDL, high-density lipoprotein; TG, triglyceride.</p

Correlations between GA/A1c ratio and other variables.

<p>Values are Pearson correlation coefficients between variables and GA/A1c ratio.</p><p>Abbreviations: NGT, normal glucose tolerance; BMI, body mass index; WHR, waist-to-hip ratio; A1c, hemoglobin A1c; GA/A1c, ratio of glycated albumin to glycated hemoglobin; LN HOMA-β, log transformed homeostasis model assessment-pancreatic beta-cell function; LN HOMA-IR, log transformed homeostatis model assessment-insulin resistance; NS, not significant.</p

Inverse Association between Glycated Albumin and Insulin Secretory Function May Explain Higher Levels of Glycated Albumin in Subjects with Longer Duration of Diabetes

<div><p>Background</p><p>Glycated albumin (GA) has been increasingly used as a reliable index for short-term glycemic monitoring, and is inversely associated with β-cell function. Because the pathophysiologic nature of type 2 diabetes (T2D) is characterized by progressive decline in insulin secretion, the aim was to determine whether GA levels were affected by diabetes duration in subjects with T2D.</p><p>Methods</p><p>To minimize the effect of glucose variability on GA, subjects with stably maintained HbA_1c levels of <0.5% fluctuation across 6 months of measurements were included. Patients with newly diagnosed T2D (<i>n</i> = 1059) and with duration>1 year (<i>n</i> = 781) were recruited and categorized as New-T2D and Old-T2D, respectively. Biochemical, glycemic, and C-peptide parameters were measured.</p><p>Results</p><p>GA levels were significantly elevated in HbA_1c-matched Old-T2D subjects compared to New-T2D subjects. Duration of diabetes was positively correlated with GA, whereas a negative relationship was found with C-peptide increment (ΔC-peptide). Among insulin secretory indices, dynamic parameters such as ΔC-peptide were inversely related to GA (<i>r</i> = −0.42, <i>p</i><0.001). Multiple linear regression analyses showed that duration of diabetes was associated with GA (standardized β coefficient [STDβ] = 0.05, <i>p</i><0.001), but not with HbA_1c (STDβ = 0.04, <i>p</i><0.095). This association disappeared after additional adjustment with ΔC-peptide (STDβ = 0.02, <i>p</i> = 0.372), suggesting that β-cell function might be a linking factor of close relationship between duration of diabetes and GA values.</p><p>Conclusions</p><p>The present study showed that GA levels were significantly increased in subjects with longer duration T2D and with decreased insulin secretory function. Additional caution should be taken when interpreting GA values to assess glycemic control status in these individuals.</p></div

Multiple logistic regression analysis to determine variables associated with GFR decline.

<p>Multiple logistic regression analysis to determine variables associated with GFR decline.</p

Effects of Omega-3 Fatty Acid Supplementation on Diabetic Nephropathy Progression in Patients with Diabetes and Hypertriglyceridemia

<div><p>Beneficial effects of omega-3 fatty acid (O3FA) supplementation in a wide range of disease condition have been well studied. However, there is limited information regarding the effects of O3FAs on chronic kidney disease (CKD), especially in diabetic nephropathy (DN) with hypertriglyceridemia. We investigate whether O3FA supplementation could help maintain renal function in patients with diabetes and hypertriglyceridemia. Total 344 type 2 diabetic patients with a history of O3FA supplementation for managing hypertriglyceridemia were included. Reduction in urine albumin to creatinine ratio (ACR) and glomerular filtrate rate (GFR) were examined. Subgroup analyses were stratified according to the daily O3FA doses. Serum total cholesterol, triglyceride, and urine ACR significantly reduced after O3FA supplementation. Overall, 172 (50.0%) patients did not experience renal function loss, and 125 (36.3%) patients had a GFR with a positive slope. The patients treated with O3FAs at 4g/day showed greater maintenance in renal function than those treated with lower dosages (p < 0.001). This dose dependent effect remains significant after adjustment for multiple variables. O3FA supplementation in diabetic patients with hypertriglyceridemia shows benefits of reducing albuminuria and maintaining renal function. The effects are dependent on the dose of daily O3FA supplementation.</p></div

Multiple linear regression analyses to determine the variables associated with HbA1c or glycated albumin.

<p>*log transformed.</p><p>STD β, standardized β coefficient; BMI, body mass index.</p><p>Multiple linear regression analyses to determine the variables associated with HbA1c or glycated albumin.</p

Baseline characteristics of study subjects.

<p>Baseline characteristics of study subjects.</p