Implementation of perioperative blood glucose monitoring and insulin infusion protocol can decrease postoperative infection rate in diabetic patients undergoing elective craniotomy: An observational study.

BACKGROUND: Severe perioperative hyperglycemia (SH) is a proven risk factor for postoperative complications after craniotomy. To reduce this risk, it has been proposed to implement the standardized clinical protocol for scheduled perioperative blood glucose concentration (BGC) monitoring. This would be followed by intravenous (IV) insulin infusion to keep BGC below 180 mg/dl in the perioperative period. The aim of this prospective observational study was to assess the impact of this type of protocol on the postoperative infection rate in patients undergoing elective craniotomy. METHODS: A total of 42 patients were prospectively enrolled in the study. Protocol included scheduled BGC monitoring in the perioperative period and rapid-acting insulin IV infusion when intraoperative SH was detected. The diagnosis of infection (wound, pulmonary, blood stream, urinary tract infection or central nervous system infection) was established according to CDC criteria within the first postoperative week. A previously enrolled group of patients with sporadic BGC monitoring and subcutaneous insulin injections for SH management was used as a control group. RESULTS: An infectious complication (i.e., pneumonia) was diagnosed only in one patient (2 %) in the prospective group. In comparison with the control group, a decrease in the risk of postoperative infection was statistically significant with OR = 0.08 [0.009 - 0.72] (p = 0.02). Implementation of the perioperative BGC monitoring and the correction protocol prevented both severe hyperglycemia and hypoglycemia with BGC < 70 mg/dl. CONCLUSION: Scheduled BGC monitoring and the use of low-dose insulin infusion protocol can decrease the postoperative infection rate in patients undergoing elective craniotomy. Future studies are needed to prove the causality of the implementation of such a protocol with an improved outcome.

Distribution of pathogens and risk factors for post-replantation wound infection in patients with traumatic major limb mutilation.

PURPOSE: Even though replantation of limb mutilation is increasing, postoperative wound infection can result in increasing the financial and psychological burden of patients. Here, we sought to explore the distribution of pathogens and identify risk factors for postoperative wound infection to help early identification and managements of high-risk patients. METHODS: Adult inpatients with severed traumatic major limb mutilation who underwent replantation from Suzhou Ruixing Medical Group between November 09, 2014, and September 6, 2022 were included in this retrospective study. Demographic, and clinical characteristics, treatments, and outcomes were collected. Data were used to analyze risk factors for postoperative wound infection. RESULTS: Among the 249 patients, 185 (74.3%) were males, the median age was 47.0 years old. Postoperative wound infection in 74 (29.7%) patients, of whom 51 (20.5%) had infection with multi-drug resistant bacteria. Ischemia time (OR 1.31, 95% CI 1.13-1.53, P = 0.001), wound contamination (OR 6.01, 95% CI 2.38-15.19, P <0.001), and stress hyperglycemia (OR 23.37, 95% CI 2.30-236.93, P = 0.008) were independent risk factors, while the albumin level after surgery (OR 0.94, 95% CI 0.89-0.99, P = 0.031) was significant associated with the decrease of postoperative wound infection. Ischemia time (OR 1.21, 95% CI 1.05-1.40, P = 0.010), wound contamination (OR 8.63, 95% CI 2.91-25.57, P <0.001), and MESS (OR 1.32, 95% CI 1.02-1.71, P = 0.037 were independent risk factors for multi-drug resistant bacteria infection. CONCLUSIONS: Post-replantation wound infection was common in patients with severe traumatic major limb mutilation, and most were multi-drug resistant bacteria. Ischemia time and wound contamination were associated with the increase of postoperative wound infection, including caused by multi-drug resistant. Positive correction of hypoproteinemia and control of stress hyperglycemia may be beneficial.

Association of persistent postoperative hyperglycemia with mortality after elective craniotomy.

OBJECTIVE: The influence of persistent postoperative hyperglycemia after craniotomy has not yet been explored. This study aimed to investigate the hypothesis that persistent postoperative hyperglycemia is associated with mortality in patients undergoing an elective craniotomy. METHODS: This study included adult patients (age ≥ 18 years) undergoing an elective craniotomy between January 2011 and March 2021 at the West China Hospital, Sichuan University. Peak daily blood glucose values measured within the first 7 days after craniotomy were collected. Persistent hyperglycemia was defined by two or more consecutive serum glucose levels of mild, moderate, or severe hyperglycemia. Normoglycemia, mild hyperglycemia, moderate hyperglycemia, and severe hyperglycemia were defined as glucose values of ≤ 6.1 mmol/L, > 6.1 and ≤ 7.8 mmol/L, > 7.8 and ≤ 10.0 mmol/L, and > 10.0 mmol/L, respectively. RESULTS: This study included 14,907 patients undergoing an elective craniotomy. In the multivariable analysis, both moderate (adjusted OR 3.76, 95% CI 2.68-5.27) and severe (adjusted OR 3.82, 95% CI 2.54-5.76) persistent hyperglycemia in patients were associated with higher 30-day mortality compared with normoglycemia. However, this association was not observed in patients with mild hyperglycemia (adjusted OR 1.32, 95% CI 0.93-1.88). Interestingly, this association was observed regardless of whether patients had preoperative hyperglycemia. There was no interaction between moderate or severe hyperglycemia and preexisting diabetes (p for interaction = 0.65). When postoperative peak blood glucose values within the first 7 days after craniotomy were evaluated as a continuous variable, for each 1-mmol/L increase in blood glucose, the adjusted OR of 30-day mortality was 1.17 (95% CI 1.14-1.21). Postoperative blood glucose (area under the curve [AUC] = 0.78) was superior to preoperative blood glucose (AUC = 0.65; p < 0.001) for predicting mortality. Moderate and severe persistent hyperglycemia in patients were associated with an increased risk of deep venous thrombosis (adjusted OR 3.20, 95% CI 2.31-4.42), pneumonia (adjusted OR 2.77, 95% CI 2.40-3.21), myocardial infarction (adjusted OR 4.38, 95% CI 3.41-5.61), and prolonged hospital stays (adjusted OR 1.43, 95% CI 1.29-1.59). CONCLUSIONS: In patients undergoing an elective craniotomy, moderate and severe persistent postoperative hyperglycemia were associated with an increased risk of mortality compared with normoglycemia, regardless of preoperative hyperglycemia.

Prednisone use, disease activity and the occurrence of hyperglycaemia and diabetes in patients with early rheumatoid arthritis: a 10-year subanalysis of the BeSt study.

OBJECTIVES: To assess whether prednisone use and/or disease activity score (DAS) are associated with the development of hyperglycaemia and diabetes in rheumatoid arthritis (RA). METHODS: We included 504 non-diabetic early RA patients from the BeSt study (Dutch acronym for treatment strategies). Patients were randomised to four DAS-steered treatment arms and followed for 10 years. The associations between DAS and prednisone use with glucose levels and the occurrence of hyperglycaemia over time were assessed with linear and logistic mixed effects regression models. Development of diabetes was analysed with Cox regression. Sensitivity analyses were performed in patients who had a first episode of hyperglycaemia. RESULTS: 31 of 504 patients (6.2%) with a mean age of 54 years developed diabetes during follow-up; 11 of these (35%) had received prior treatment with prednisone. Prednisone use was not associated with development of hyperglycaemia or diabetes after correction for multiple testing in main or sensitivity analyses. In the main analyses, DAS was significantly associated with development of diabetes (HR 1.802 per 1 point DAS increase, 95% CI 1.284 to 2.529) but not with glucose levels nor hyperglycaemia. In patients with previous hyperglycaemia, DAS was associated with glucose levels, recurrence of hyperglycaemia and diabetes. CONCLUSIONS: In non-diabetic early RA patients, the use of prednisone was not associated with developing hyperglycaemia or diabetes. However, high DAS increased the risk of diabetes. Potential risks associated with prednisone use may have been mitigated by its effect on DAS.

Time matters: an insight into the relationship between chrononutrition and diabetes.

Chrononutrition is a branch of chronobiology that evaluates nutrients and the pathways implicated in their regulation in accordance with circadian rhythms. Sleep deprivation and disturbances have been strongly associated with the progression of different metabolic alterations, and the time of food intake plays a fundamental role in maintaining metabolic homeostasis. It has been demonstrated that not only the components of food are important, but quantity and quality are also crucial elements of a healthy eating pattern. Chrononutrition is an emerging tool that could help improve dietary interventions beyond those derived from consuming an adequate amount of each nutrient. Diabetes is a complex endocrine pathology characterized by sustained hyperglycemia. Dietary changes are a key component in obtaining adequate control and preventing long-term complications. Recent studies emphasize the use of chrononutrition and its components as a novel dietary intervention that could improve metabolic control. The use of chrononutrition as a dietary intervention is faced with challenges such as the presence of gaps in the literature that limit its implementation. This emphasizes the imperative need for additional research that can lead to an evidence-based use of this intervention.

Stress hyperglycemia is associated with poor outcome in critically ill patients with pulmonary hypertension.

Background and objective: Stress hyperglycemia is common in critically ill patients and is associated with poor prognosis. Whether this association exists in pulmonary hypertension (PH) patients is unknown. The present cohort study investigated the association of stress hyperglycemia with 90-day all-cause mortality in intensive care unit (ICU) patients with PH. Methods: Data of the study population were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. A new index, the ratio of admission glucose to HbA1c (GAR), was used to evaluate stress hyperglycemia. The study population was divided into groups according to GAR quartiles (Q1-Q4). The outcome of interest was all-cause mortality within 90 days, which was considered a short-term prognosis. Result: A total of 53,569 patients were screened. Ultimately, 414 PH patients were enrolled; 44.2% were male, and 23.2% were admitted to the cardiac ICU. As the GAR increased from Q2 to Q4, the groups had lower creatinine levels, longer ICU stays, and a higher proportion of renal disease. After adjusting for confounding factors such as demographics, vital signs, and comorbidities, an elevated GAR was associated with an increased risk of 90-day mortality. Conclusion: Stress hyperglycemia assessed by the GAR was associated with increased 90-day mortality in ICU patients with PH.

An effective insulin infusion protocol for severe traumatic brain injury patients: A retrospective observational study.

PURPOSE: Severe traumatic brain injury (sTBI) patients often experience stress hyperglycaemia, which can lead to negative outcomes. This study aims to introduce an effective insulin infusion protocol specifically designed for sTBI patients. METHODS: Data was collected from all sTBI patients during two periods: 1 October 2019 to 30 April 2020, and 1 June 2020 to 31 December 2020. In May 2020, a new insulin infusion protocol was implemented. Blood glucose management, infection, coagulation, and prognosis were compared in these two periods. RESULT: 195 patients were included, with 106 using the new protocol. The proportion of hyperglycaemia decreased from 40.04% to 26.91% (P<0.05), and the proportion of on-target blood glucose levels increased from 35.69% to 38.98% (P<0.05). Average blood glucose levels decreased from 9.98±2.79mmol/L to 8.96±2.82mmol/L (P<0.05). There was no substantial increase in hypoglycaemia, which remained controlled below 1%. The new protocol positively influenced glucose concentration and dispersion trends. There were no significant differences in catheter-related infections, antibiotic use, mechanical ventilation (MV) duration, length of stay in ICU, Glasgow Outcome Scale (GOS), or mortality. However, the conventional protocol group had a higher coagulation tendency (R-value of thromboelastography 4.80±1.35min vs. 5.52±1.87min, P<0.05), with no difference in deep vein thrombosis (DVT) incidence. CONCLUSION: Our findings suggest that a customized insulin infusion process for sTBI patients can effectively manage blood glucose. While there is no significant improvement in infection control or prognosis, it may have a positive impact on coagulation without affecting the occurrence of DVT.

Accelerated onset of diabetes in non-obese diabetic mice fed a refined high-fat diet.

AIM: Type 1 diabetes results from autoimmune events influenced by environmental variables, including changes in diet. This study investigated how feeding refined versus unrefined (aka 'chow') diets affects the onset and progression of hyperglycaemia in non-obese diabetic (NOD) mice. METHODS: Female NOD mice were fed either unrefined diets or matched refined low- and high-fat diets. The onset of hyperglycaemia, glucose tolerance, food intake, energy expenditure, circulating insulin, liver gene expression and microbiome changes were measured for each dietary group. RESULTS: NOD mice consuming unrefined (chow) diets developed hyperglycaemia at similar frequencies. By contrast, mice consuming the defined high-fat diet had an accelerated onset of hyperglycaemia compared to the matched low-fat diet. There was no change in food intake, energy expenditure, or physical activity within each respective dietary group. Microbiome changes were driven by diet type, with chow diets clustering similarly, while refined low- and high-fat bacterial diversity also grouped closely. In the defined dietary cohort, liver gene expression changes in high-fat-fed mice were consistent with a greater frequency of hyperglycaemia and impaired glucose tolerance. CONCLUSION: Glucose intolerance is associated with an enhanced frequency of hyperglycaemia in female NOD mice fed a defined high-fat diet. Using an appropriate matched control diet is an essential experimental variable when studying changes in microbiome composition and diet as a modifier of disease risk.

Detection and Management of Perioperative Hyperglycemia at a Tertiary Cancer Center.

INTRODUCTION: To improve the detection and management of perioperative hyperglycemia at our tertiary cancer center, we implemented a glycemic control quality improvement initiative. The primary goal was to decrease the percentage of diabetic patients with median postoperative glucose levels > 180 mg/dL during hospitalization by 15% within 2 years. METHODS: A multidisciplinary team standardized preoperative screening, preoperative, intraoperative, and postoperative hyperglycemia management. We included all patients undergoing nonemergent inpatient and outpatient operations. We used a t test, rank sum, chi-square, or Fisher's exact test to assess differences in outcomes between patients at baseline (BL) (10/2018-4/2019), during the first phase (P1) (10/2019-4/2020), second phase (P2) (5/2020-12/2020), and maintenance phase (M) (1/2021-10/2022). RESULTS: The analysis included 9891 BL surgical patients (1470 with diabetes), 8815 P1 patients (1233 with diabetes), 10,401 P2 patients (1531 with diabetes) and 30,410 M patients (4265 with diabetes). The percentage of diabetic patients with median glucose levels >180 mg/dL during hospitalization decreased 32% during the initiative (BL, 20.1%; P1, 16.9%; P2, 12.1%; M, 13.7% [P < .001]). We also saw reductions in the percentages of diabetic patients with median glucose levels >180 mg/dL intraoperatively (BL, 34.0%; P1, 26.6%; P2, 23.9%; M, 20.3% [P < .001]) and in the postanesthesia care unit (BL, 36.0%; P1, 30.4%; P2, 28.5%; M, 25.8% [P < .001]). The percentage of patients screened for diabetes by hemoglobin A1C increased during the initiative (BL, 17.5%; P1, 52.5%; P2, 66.8%; M 74.5% [P < .001]). CONCLUSIONS: Our successful initiative can be replicated in other hospitals to standardize and improve glycemic control among diabetic surgical patients.

Effects of admission hyperglycemia and intravenous thrombolysis allocation in acute basilar artery occlusion after endovascular treatment: Analysis of the ATTENTION registry.

This study was to investigate the admission hyperglycemia and modified effect of intravenous thrombolysis (IVT) on clinical outcomes in acute basilar artery occlusion (BAO) patients receiving endovascular treatment (EVT). We prospectively recruited acute BAO patients from 48 stroke centers across 22 Chinese provinces in the ATTENTION registry from 2017 to 2021. Hyperglycemia on admission was defined as glucose ≥7.8 â€‹mmol/L. We performed multivariable logistic regression analysis to evaluate the correlation of hyperglycemia on admission with the primary outcome defined as a modified Rankin scale (mRS) score of <4 â€‹at 90 days, and the secondary outcomes defined as successful recanalization, mRS 0-1 and 0-2 â€‹at 90 days. Safety outcomes were symptomatic intracranial hemorrhage (sICH) and mortality within 90 days. There were 1195 patients with acute BAO treated with EVT of whom 519 had hyperglycemia on admission. Hyperglycemia on admission was inversely associated with favorable neurological outcomes (mRS 0-3: adjusted odd ratio [aOR] 0.69, 95 â€‹% confidence intervals [CI] 0.54-0.89, P â€‹= â€‹0.004; mRS 0-1: aOR 0.67, 95 â€‹% CI 0.50-0.90, P â€‹= â€‹0.008; mRS 0-2: aOR 0.73, 95 â€‹% CI 0.56-0.95; P â€‹= â€‹0.02). Hyperglycemia on admission was not correlated to sICH nor successful recanalization. In the subgroup of BAO patients treated with direct EVT, those with hyperglycemia on admission had a higher mortality rate, and overall worse clinical outcomes at 90 days than patients without hyperglycemia. A significant interaction was observed between IVT and hyperglycemia on admission (Pinteraction â€‹= â€‹0.017). In patients with acute BAO treated with EVT, hyperglycemia on admission was associated with worse functional outcomes at 90 days but was not correlated with sICH nor successful recanalization. The effect of admission hyperglycemia appears to be modified by IVT allocation. Unique identifier: ChiCTR2000041117.

Differential Association between Blood Glucose Levels and Nonrelapse Mortality after Allogeneic Hematopoietic Cell Transplantation Based on Presence or Absence of Preexisting Diabetes.

Malglycemia, defined as hyperglycemia, hypoglycemia, or increased glycemic variability, has been associated with increased mortality after allogeneic hematopoietic cell transplantation (HCT). Among critically ill non-HCT recipients with diabetes and poor glycemic control, compared to those without diabetes, stringent blood glucose control has been associated with increased mortality. This study investigated whether a pre-HCT diagnosis of diabetes and the type of pre-HCT diabetes treatment modulate the previously reported negative impact of malglycemia on post-HCT nonrelapse mortality (NRM). We performed a single-institution retrospective analysis of mortality outcomes after allogeneic HCT as a function of post-HCT blood glucose levels, pre-HCT diagnosis of diabetes, and type of pre-HCT diabetes treatment (insulin, no insulin). A total of 1062 patients who underwent allogeneic HCT between 2015 and 2020 were included in this study. Among these patients, 84 (8%) had a pre-HCT diagnosis of diabetes, of whom 38 (4%) used insulin and 46 (4%) used a noninsulin antiglycemic agent. Post-HCT blood glucose values measured within 100 days from HCT, modeled as a continuous nonlinear time-varying covariate, were associated with day-200 NRM, with both lower and higher glycemic values associated with higher NRM compared to normoglycemic values (adjusted P < .0001). The association between post-HCT blood glucose and NRM varied, however, depending on the presence or absence of a pre-HCT diagnosis of diabetes; that is, there was evidence of a statistical interaction between blood glucose levels and diabetes (adjusted P = .008). In particular, the detrimental impact of hyperglycemic values was more pronounced in patients without a pre-HCT diagnosis of diabetes compared to those with a pre-HCT diagnosis of diabetes. As reported previously, higher and lower blood glucose levels measured within 100 days after allogeneic HCT were associated with an increased risk of NRM; however, this association was more pronounced among patients without a pre-HCT diagnosis of diabetes compared to those with a pre-HCT diagnosis of diabetes, suggesting that patients with diabetes are relatively protected from the downstream effects of hyperglycemia. These data support the notion that patients with pre-HCT diabetes may need a different approach to blood glucose management after transplantation compared to those without diabetes. © 2024 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

Early post-transplant hyperglycemia and post-transplant diabetes mellitus following heart transplantation.

INTRODUCTION: Heart transplantation is an important treatment for end-stage heart failure. Early post-transplant hyperglycemia (EPTH) and post-transplant diabetes mellitus (PTDM) are common following heart transplantation and are associated with increased morbidity and mortality. AREAS COVERED: This review summarizes the clinical characteristics, diagnosis, and treatment of EPTH and PTDM in cardiac transplant patients, incorporating findings from non-cardiac solid organ transplant studies where relevant due to limited heart-specific research. EXPERT OPINION: EPTH following heart transplantation is common yet understudied and is associated with the later development of PTDM. PTDM is associated with adverse outcomes including infection, renal dysfunction, microvascular disease, and an increased risk of re-transplantation and mortality. Risk factors for EPTH include the post-operative immunosuppression regimen, recipient and donor age, body mass index, infections, and chronic inflammation. Early insulin treatment is recommended for EPTH, whereas PTDM management is varied and includes lifestyle modification, anti-glycemic agents, and insulin. Given the emerging evidence on the transplant benefits associated with effective glucose control, and the cardioprotective potential of newer anti-glycemic agents, further focus on the management of EPTH and PTDM within heart transplant recipients is imperative.

Total Pancreatectomy in a Patient Treated with a Sensor-augmented Pump Showing No Evidence of Hyperglycemia or Ketoacidosis without Any Insulin Administration.

Total pancreatectomy results in complete loss of insulin and glucagon. Sensor-augmented pumps (SAPs) allow fine-tuning of the basal insulin rate, which helps avoid both hypo- and hyperglycemic events. We herein report a case of total pancreatectomy treated with a SAP with no evidence of ketoacidosis without any insulin administration during a certain period of time. Furthermore, we observed a sudden drop in blood glucose levels without insulin, which may have been due to glucose effectiveness. Our case is valuable in arguing the concept of glucose effectiveness in the absence of insulin and glucagon.

Supporting Type 1 and Type 2 Diabetes Care in the Hemodialysis Unit: A Quality-improvement Initiative Throughout the COVID-19 Pandemic.

OBJECTIVE: People living with diabetes mellitus (DM) and chronic kidney disease can have difficulty attending multiple appointments to receive DM care. We developed and studied the utility of a DM outreach program to offer in the hemodialysis (HD) unit. METHODS: We conducted a quality improvement project in a satellite HD unit in London, Ontario, Canada, between August 1, 2019, and July 31, 2022. We assessed for baseline gaps in DM care among those with DM, performed root-cause analysis with key stakeholders to identify critical drivers of gaps, and conceptualized a certified diabetes educator-led outreach program to offer in the HD unit. We aimed to improve DM self-monitoring, hypo- and hyperglycemia, and DM-related screening. We used run and control charts to track outcome measures over time and modified our outreach program iteratively. RESULTS: Fifty-eight persons with DM receiving HD participated in our program. Support spanned multiple waves of the COVID-19 pandemic. With 4 tests of change, we observed improvement in DM self-monitoring with a modest decline in self-reported hyperglycemia. There were no adverse consequences, and satisfaction with our program was high. CONCLUSIONS: Although we did not meet all measures of success during the pandemic, outreach DM support in the HD unit appeared to improve self-monitoring and self-reported hyperglycemia. Similar programs could be modified and implemented in other centres.

Parenteral nutrition-related complications in older patients with acute intestinal failure: A descriptive cohort study.

INTRODUCTION: Reported outcomes for parenteral nutrition (PN)-related complications in older adult patients with acute intestinal failure who are receiving PN in the acute hospital setting are limited. Our study aims to compare PN-related complications between older and younger adult patients. METHODS: A retrospective descriptive study of inpatients who were administered PN from January 1, 2019, to December 31, 2019, was performed. Patients were categorized into older (≥65 years old) and younger (<65 years old) adult groups. RESULTS: Two hundred thirty-five patients were included. There were 103 patients in the older adult group (mean age: 73.9 [SD: 6.9] years) and 132 patients in the younger adult group (mean age: 52.4 [SD: 12.5] years). There was a significantly higher Charlson Comorbidity Index score and lower Karnofsky score in the older adult group. The older adult group received significantly lower total energy (20.8 [SD: 7.8] vs 22.8 [SD: 6.3] kcal/kg/day), dextrose (3.1 [SD: 1.4] vs 3.6 [SD: 1.4] g/kg/day), and protein (1.1 [SD: 0.4] vs 1.2 [SD: 0.3] g/kg/day) than the younger group received. The mean length of stay was significantly shorter in the older adult group (35.9 [SD: 21.3] vs 59.8 [SD: 55.3]; P < 0.05). There was no significant difference in PN-related complications and clinical outcomes (catheter-related bloodstream infections, hypoglycemia or hyperglycemia, fluid overload, or inpatient mortality) between the two groups. CONCLUSION: Despite more comorbidities in the older adult, the usage of PN in older adult patients with acute intestinal failure was associated with neither an increased rate of PN-related complications nor worse clinical outcomes when compared with that of younger patients.

Reductions in liver enzymes are associated with anti-hyperglycaemic and anti-obesity effects of tofogliflozin in people with type 2 diabetes: Post-hoc analyses.

AIMS: How the pathology of type 2 diabetes (T2D), including hyperglycaemia and obesity, affects liver enzymes has not been clinically demonstrated. Thus, we compared time courses of gamma-glutamyltransferase (GGT) and alanine aminotransferase (ALT) with those of fasting plasma glucose (FPG) and body weight (BW) during treatment with the SGLT2 inhibitor tofogliflozin for T2D. MATERIALS AND METHODS: We post-hoc analysed preexisting data on 1046 people with T2D administered tofogliflozin or placebo for 24 weeks in four tofogliflozin studies. First, time courses of percent changes in variables during the intervention were analysed using a mixed effect model to explore the similarity of the time courses and to evaluate time-treatment interactions. Second, clinical factors related to the percent changes in GGT and ALT were clarified using multivariate analyses. RESULTS: GGT levels and FPG values rapidly and significantly decreased via tofogliflozin as early as week 4, with decreases maintained until week 24. Conversely, BW and ALT decreased progressively until week 24. Time courses of FPG (p = .365, time-treatment interaction) and GGT (p = .510) reductions were parallel between tofogliflozin and placebo from weeks 4 to 24, while BW and ALT reductions (p < .001, respectively) were not. Reductions in GGT at week 24 were associated with reductions in FPG and BW at week 24, whereas ALT reductions were only associated with reductions in BW. CONCLUSIONS: Reductions in GGT and ALT were associated with the anti-hyperglycaemic and anti-obesity effects of tofogliflozin, respectively, in people with T2D. Therefore, GGT and ALT may be surrogate markers for hyperglycaemia and obesity in T2D.