The Relationship between Increases in Morning Spot Urinary Glucose Excretion and Decreases in HbA1C in Patients with Type 2 Diabetes After Taking an SGLT2 Inhibitor: A Retrospective, Longitudinal Study

<p><strong>Article full text</strong></p> <p><br> The full text of this article can be found <a href="https://link.springer.com/article/10.1007/s13300-017-0248-5"><b>here</b>.</a><br> <br> <strong>Provide enhanced digital features for this article</strong><br> If you are an author of this publication and would like to provide additional enhanced digital features for your article then please contact <u>[email protected]</u>.<br> <br> The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.<br> <br> Other enhanced features include, but are not limited to:<br> • Slide decks<br> • Videos and animations<br> • Audio abstracts<br> • Audio slides<u></u></p

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

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

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

Data_Sheet_1_Combining SGLT2 Inhibition With a Thiazolidinedione Additively Attenuate the Very Early Phase of Diabetic Nephropathy Progression in Type 2 Diabetes Mellitus.pdf

<p>Although both sodium glucose co-transporter 2 inhibition by dapagliflozin and thiazolidinedione, pioglitazone have glucose-lowering and anti-inflammatory effects, the therapeutic efficacy of their combination on diabetic nephropathy has not been investigated. 9-week-old male db/db mice were randomly assigned to 4 groups and administrated with (1) vehicle, (2) dapagliflozin, (3) pioglitazone, or (4) dapagliflozin and pioglitazone combination. Human proximal tubule (HK-2) cells were treated with glucose or palmitate acid in the presence of medium, dapagliflozin, pioglitazone, or both. Glomerular tuft area and mesangial expansion of the kidney more reduced in the combination group compared to control and single therapy groups. Podocyte foot process width and glomerular basement membrane thickness decreased regardless of treatment, while the combination group showed the slowest renal hypertrophy progression (P < 0.05). The combination treatment decreased MCP-1, type I and IV collagen expression in the renal cortex. Only the combination treatment decreased the expression of angiotensinogen, IL-6, and TGF-β while it enhanced HK-2 cell survival (all P < 0.05). In conclusion, dapagliflozin and pioglitazone preserved renal function, and combination therapy showed the greatest benefit. These findings suggest that the combination therapy of dapagliflozin with pioglitazone is more effective than the single therapy for preventing the progression of nephropathy in patients with type 2 diabetes.</p

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

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

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

Baseline characteristics of study subjects.

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

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

Differences of glycated albumin (GA) and GA/HbA_1c ratios according to the duration of diabetes by HbA_1c ranges.

<p>(<b>A</b>) glycated albumin; (<b>B</b>) GA/HbA_1c ratio. Data are shown as mean with SD (bars). *P<0.001 compared to those from subjects with New-T2D.</p