Stewart B Harris’s research while affiliated with Western University and other places

Aim We aimed to investigate glycated haemoglobin (HbA1c) levels and healthcare resource utilization (HCRU; emergency department [ED] visits or hospitalization) before and after adoption of FreeStyle Libre sensor‐based glucose monitoring systems (FSL) by people with type 2 diabetes mellitus (T2DM) on basal insulin without glucagon‐like peptide 1 receptor agonist (GLP‐1 RA) therapy, basal insulin with GLP‐1 RA therapy, GLP‐1 RA therapy without insulin or oral therapy alone. Materials and Methods Routinely collected administrative health data (housed at IC/ES, formerly the Institute for Clinical Evaluative Sciences) in Ontario, Canada were used to identify 20 253 people with T2DM who had a first FSL claim between 16 September 2019 and 31 August 2020 (index date) and remained active on FSL for 24 months' follow‐up. HCRU was measured for 12 months before the index date and the last 12 months of the 24‐month follow‐up period. HbA1c data were taken from the latest tests in each period. Results Mean HbA1c was statistically significantly reduced after FSL acquisition among people aged ≤65 or >65 years in all four treatment groups (range, 0.3–0.8% reduction). After FSL acquisition, ED visits and hospitalization were statistically significantly reduced in the oral therapy only group and in some basal insulin subgroups (without GLP‐1 RA, all except hospitalization aged ≤65 years; with GLP‐1 RA, only ED visits aged ≤65 years). Conclusions Among people with T2DM using basal insulin and/or non‐insulin therapies, HbA1c levels were statistically significantly improved and HCRU was reduced after initiation of FSL.

Background: Evidence suggests that dairy-derived saturated and trans fatty acids may contribute to observed inverse associations of dairy intake with risk of metabolically associated fatty liver disease (MAFLD) and type 2 diabetes mellitus (T2DM). Longitudinal studies examining the association between circulating dairy fatty acids and phenotypes underlying these disorders are limited. This study aimed to investigate the 9-year longitudinal associations of 15:0 (pentadecanoic acid), t16:1n9 (trans palmitoleic acid), t18:1n11 (trans vaccenic acid) and c9,t11 CLA (conjugated linoleic acid) in four serum fractions with insulin sensitivity, beta cell function and alanine aminotransferase (ALT in U/L, a biomarker of liver function). Methods: In the PROMISE cohort (n=460), insulin sensitivity was assessed using Matsuda’s insulin sensitivity index (ISI) and the homeostasis model assessment of insulin sensitivity (HOMA2_S). Beta cell function was determined using the insulinogenic index divided by HOMA insulin resistance (IGI/IR) and the Insulin Secretion-Sensitivity Index-2 (ISSI-2). Serum ALT was measured at each visit. Baseline serum fatty acids (mol%) in the cholesteryl ester (CE), non-esterified fatty acid (NEFA), phospholipid (PL) and triglyceride (TG) pools were analyzed using gas chromatography flame-ionization detection. Longitudinal associations were analyzed using covariate-adjusted generalized estimating equations with P values adjusted using the Benjamini-Hochberg False Discovery Rate (FDR). Results: In the TG pool, 18:1n11t was significantly associated with logISSI-2 (β= 3.09, CI: [0.04, 6.24], p<0.05). Significant inverse associations were observed between 15:0 (CE) and logALT (β= -3.30, CI: [-5.33, -1.24], p<0.01). In the PL pool, 15:0 was positively associated with logISSI-2 (β=5.37, CI: [1.71, 9.16], p<0.01) and logIGI/IR (β=10.49, CI: [4.35, 16.99], p<0.01). After FDR adjustment, 15:0 (CE) continued to be inversely associated with logALT (p<0.05). Similarly, 15:0 (PL) was significantly associated with logISSI-2 and logIGI/IR (p<0.05). Fatty acids in the NEFA and TG pools were not significantly associated with outcomes. Conclusions: Longitudinal associations of dairy-derived serum fatty acids with liver health and beta cell function were detected across serum pools. Our findings expand the literature on the potential role of dairy-derived saturated and trans conjugate fatty acids in cardiometabolic phenotypes underlying MAFLD and T2DM.

Background: Literature on omega-3s and T2D risk has been heterogenous; however, most prior studies have used self-reported dietary intake or short-term supplementation regimens. Thus, further investigation is needed to assess longitudinal associations of circulating omega-3 with early T2D risk phenotypes. Objective: Assess longitudinal associations of circulating omega-3s with changes in insulin sensitivity (IS) and β-cell function (BCF) in the PROMISE cohort. Methods: Adults at-risk for T2D underwent four assessments over 9 years (n=472); blood samples were collected to determine insulin and glucose concentrations, and an OGTT was conducted. Baseline serum omega-3s (ALA, EPA, DPAn-3, DHA) were measured using gas chromatography-flame ionization detection. OGTT values were used to calculate validated IS (HOMA2-%S, ISI) and BCF (IGI/IR, ISSI-2) indices. Generalized estimating equations (GEE) analysis assessed the association between baseline omega-3s (mol%) with longitudinal change in IS and BCF indices after covariate adjustment. Results: Significant positive correlations were shown between EPA and DHA with IS measures (HOMA2-%S: EPA, r=0.18, DHA, r=0.23, all p<0.001; ISI: EPA, r=0.15, p<0.01, DHA, r=0.19, p<0.001) and between DHA and BCF indices (IGI/IR, r=0.14, p<0.01; ISSI-2, r=0.1, p<0.05). In adjusted GEE models, baseline EPA and DHA were positively associated with longitudinal change in IS (HOMA2-%S, p<0.001; ISI , p<0.01), and BCF (IGI/IR, p<0.05) ( Figure ) . Conclusions: Circulating omega-3s (specifically EPA and DHA) were positively associated with IS and BCF, which are important early T2D risk phenotypes. These findings add to growing evidence of the potential role omega-3s have in T2D primary prevention.

Background: Diabetes mellitus is associated with significant health care resource utilization (HCRU), partly due to acute complications, including diabetic ketoacidosis (DKA) and hypoglycemia. Aim: To investigate glycated hemoglobin (HbA1c) levels and HCRU before and after adoption of FreeStyle Libre Systems (FSL) in people with diabetes on multiple daily injections of insulin (MDI). Methods: This retrospective longitudinal study used administrative health data in Ontario, Canada, housed at IC/ES. The cohort comprised people with diabetes on MDI with a first FSL claim between September 16, 2019, and August 31, 2020 (index date), who remained on FSL for 24 months. HCRU (emergency department [ED] visits and hospitalization) was measured for 12 months before the index date and the last 12 months of follow-up. HbA1c data were taken from the last tests in each period. Results: Mean HbA1c was statistically significantly reduced after FSL among people with type 1 diabetes mellitus (T1DM; n = 10,510; age <25 years, -0.8%; 25-65 years, -0.5%; >65 years, -0.1%; all P < 0.0001) or type 2 diabetes mellitus (T2DM; n = 12,668; age ≤65 years, -0.6%; >65 years, -0.3%; both P < 0.0001). Overall HCRU was statistically significantly reduced in the T1DM subgroups aged <25 and 25-65 years (ED visits only) and both T2DM age subgroups, with some subgroups having statistically significant reductions in DKA- or hypoglycemia-associated HCRU. Conclusions: Among people with T1DM or T2DM on MDI, HbA1c was statistically significantly reduced after FSL, with statistically significant reductions in HCRU in some subgroups.

Context Statin treatment lowers low-density lipoprotein (LDL) cholesterol thereby reducing cardiovascular risk. Meta-analyses of clinical trials report a higher risk of new-onset type 2 diabetes with statins. Current clinical evidence regarding effects of statins on insulin sensitivity and beta-cell function is limited. Objective We examined the effects of statin treatment on longitudinal changes in early risk phenotypes for type 2 diabetes. Methods The PROMISE cohort is a longitudinal study of adults at-risk for type 2 diabetes. Data from baseline and 3 follow-up visits over 9 years were used to estimate insulin sensitivity (ISI, HOMA2-%S) and beta-cell function (IGI/IR, ISSI-2). Statin use was self-reported. Associations of statins with changes in metabolic markers were determined through Generalized Estimating Equations. Results Over 9 years, 169 of 498 participants (50 years, 74% female) received a statin, predominantly rosuvastatin and atorvastatin. Compared to no statin treatment, statin users had lower insulin sensitivity (5.32-6.36%) and beta-cell function (4.93-7.59%) (p<0.001) adjusting for metabolic risk factors. Rosuvastatin was associated with decreased insulin sensitivity and beta-cell function, while atorvastatin showed moderate inverse association with beta-cell function and insulin sensitivity. In females, statins reduced insulin sensitivity and beta-cell function, while in males only beta-cell function was altered. Conclusion Statin treatment was associated with lowered insulin sensitivity and beta-cell function with potential differential effects among statin agents and the sexes.

For people living with diabetes, effective glucose monitoring is a key component in diabetes care, helping to reduce disease burden, complications, and healthcare utilization. Sensor-based glucose monitoring systems, which can provide more comprehensive information about glucose levels than capillary-based self-monitoring of blood glucose (SMBG), are becoming established among people living with diabetes. The objective of this study was to assess the cost-effectiveness of glucose monitoring with FreeStyle Libre systems, compared with SMBG, from the perspective of a Canadian private payer. The analysis used the validated, person-level microsimulation model DEDUCE (Determination of Diabetes Utilities, Costs, and Effects). Analyses were conducted separately for populations of people with type 1 and type 2 diabetes mellitus (T1DM; T2DM), with time horizons of 40 and 25 years, respectively. T2DM treatment was assumed to be 84% non-insulin, 10% basal insulin, and 6% multiple daily injections of insulin. The effect of FreeStyle Libre was modeled as reductions versus SMBG in glycated hemoglobin level (T1DM, − 0.42%; insulin-treated T2DM, − 0.59%; non-insulin-treated T2DM, − 0.3%) and in acute diabetic events (hypoglycemia and diabetic ketoacidosis). Costs (in 2023 Canadian dollars (Can$)) and utilities were discounted at 1.5In both populations, FreeStyle Libre was dominant to SMBG, providing more QALYs at a lower cost (T1DM: + 1.25 QALYs, − Can$32,287 costs; T2DM: + 0.48 QALYs, − Can$8091 costs). Reductions were seen in the cumulative incidence of all complications (except blindness in the T1DM analysis). FreeStyle Libre was dominant to SMBG in all scenarios tested. Probabilistic sensitivity analysis showed that FreeStyle Libre had a 100% probability of being dominant to SMBG for T1DM and a 91% probability of being dominant for T2DM. This economic analysis shows that, from a Canadian private payer perspective, FreeStyle Libre is cost-effective compared with SMBG for all people living with diabetes.

Aims: When administered in early type 2 diabetes (T2DM), the strategy of 'induction' with short-term intensive insulin therapy (IIT) followed by 'maintenance' with metformin thereafter can yield outstanding glycaemic control, with some patients achieving A1c in the normal range of its assay. We thus sought to identify determinants of sustained normalisation of A1c in response to this treatment strategy. Materials and methods: In this study, adults with T2DM of mean duration 1.7 ± 1.4 years received induction IIT (glargine, lispro) for 3 weeks, followed by metformin maintenance either with or without periodic 2-week courses of IIT every 3 months for 2 years. Sustained glycaemic normalisation was defined by A1c <6.0% at 2 years. Results: Of 101 participants, 26 achieved A1c <6.0% at 2 years. At baseline, these individuals had lower A1c and fasting glucose than the other participants, along with better beta-cell function. During maintenance therapy from 3 weeks to 2 years, they had greater reduction of adiposity (body mass index: p = 0.02; waist circumference: p = 0.02), hepatic insulin resistance (HOMA-IR: p = 0.02) and ALT (p = 0.005), coupled with relative stabilisation of beta-cell function and glycaemia. On logistic regression analyses, significant independent predictors of normalisation of A1c at 2 years were baseline A1c (adjusted odds ratio [aOR] = 0.01 [95% CI 0.001-0.16], p = 0.001) and the changes in waist circumference (aOR = 0.77 [0.63-0.94], p = 0.012) and ALT (aOR = 0.90 [0.82-0.98], p = 0.019) during maintenance therapy from 3 weeks to 2 years. Conclusions: While lower baseline A1c and greater reduction in central adiposity predicted A1c <6.0% at 2 years as anticipated, the emergence of greater reduction in ALT as a concomitant determinant highlights the role of the liver in the achievement of sustained glycaemic normalisation.