Real-world lived experience of older adults with type 1 diabetes after an automated insulin delivery trial.

AIMS: First-generation closed-loop automated insulin delivery improves glycaemia and psychosocial outcomes among older adults with type 1 diabetes in clinical trials. However, no study has previously assessed real-world lived experience of older adults using closed-loop therapy outside a trial environment. METHODS: Semi-structured interviews were conducted with older adults who were pre-existing insulin pump users and previously completed the OldeR Adult Closed-Loop (ORACL) randomised trial. Interviews focused on perceptions of diabetes technology use, and factors influencing decisions regarding continuation. RESULTS: Twenty-eight participants, mean age 70 years (SD 5), were interviewed at median 650 days (IQR 608-694) after their final ORACL trial visit. At interview, 23 participants (82%) were still using a commercial closed-loop system (requiring manual input for prandial insulin bolus doses). Themes discussed in interviews relating to closed-loop system use included sustained psychosocial benefits, cost and retirement considerations and usability frustrations relating to sensor accuracy and system alarms. Of the five participants who had discontinued, reasons included cost, continuous glucose monitoring-associated difficulties and usability frustrations. Cost was the largest consideration regarding continued use; most participants considered the increased ease of diabetes management to be worth the associated costs, though cost was prohibitive for some. CONCLUSIONS: Almost 2 years after completing a closed-loop clinical trial, closed-loop automated insulin delivery remains the preferred type 1 diabetes therapy for the majority of older adult participants. Chronological age is not a barrier to real-world successful use of diabetes technology. Identifying age-related barriers, and solutions, to diabetes technology use among older adults is warranted.

Lived experience of older adults with type 1 diabetes using closed-loop automated insulin delivery in a randomised trial.

AIM: To explore the lived experience of older adults with type 1 diabetes using closed-loop automated insulin delivery, an area previously receiving minimal attention. METHODS: Semi-structured interviews were conducted with adults aged 60 years or older with long-duration type 1 diabetes who participated in a randomised, open-label, two-stage crossover trial comparing first-generation closed-loop therapy (MiniMed 670G) versus sensor-augmented pump therapy. Interview recordings were transcribed, thematically analysed and assessed. RESULTS: Twenty-one older adults participated in interviews after using closed-loop therapy. Twenty were functionally independent, without frailty or major cognitive impairment; one was dependent on caregiver assistance, including for diabetes management. Quality of life benefits were identified, including improved sleep and reduced diabetes-related psychological burden, in the context of experiencing improved glucose levels. Gaps between expectations and reality of closed-loop therapy were also experienced, encountering disappointment amongst some participants. The cost was perceived as a barrier to continued closed-loop access post-trial. Usability issues were identified, such as disruptive overnight alarms and sensor inaccuracy. CONCLUSIONS: The lived experience of older adults without frailty or major cognitive impairment using first-generation closed-loop therapy was mainly positive and concordant with glycaemic benefits found in the trial. Older adults' lived experience using automated insulin delivery beyond trial environments requires exploration; moreover, the usability needs of older adults should be considered during future device development.

Insulin antibodies are prevalent in adults with type 1 diabetes referred for islet cell transplantation and are modified by islet transplantation and immunosuppression: an Australian experience.

We have analysed insulin antibodies in 149 adults with type 1 diabetes and 2859 people without diabetes. We have determined that insulin antibody levels are higher in adults with, versus without, diabetes and that the levels are falling, and more patients are becoming antibody-negative post islet cell transplantation.

Bridging the gap between diabetes care and mental health: perspectives of the Mental health IN DiabeteS Optimal Health Program (MINDS OHP).

BACKGROUND: Mental health problems are highly prevalent in people with type 1 diabetes mellitus (T1DM), which adversely impact physical health and quality of life. This study aimed to explore the experiences of people with T1DM who had completed the Mental health IN DiabeteS Optimal Health Program (MINDS OHP), a novel intervention developed to bridge the gap between physical and mental health care. METHOD: Participants with T1DM were invited to take part in a focus group or semi-structured interviews. Participants were recruited from outpatient and community settings. The focus group and interviews were audio-recorded and transcribed verbatim. Thematic content analysis was used and identified themes were cross-validated by researchers and member-checked by participants. RESULTS: Ten people with T1DM were included. Two key themes emerged: 'MINDS OHP experiences' and 'lived experiences of diabetes'. MINDS OHP experiences included five sub-themes: program benefits, follow-up and timing, suggested improvements, collaborative partners, and materials suitability. Lived experiences also included five sub-themes: bridging the gap between mental and physical health, support networks, stigma and shame, management intrusiveness, and adolescence and critical life points. CONCLUSIONS: The MINDS OHP for people with T1DM was generally well received, though study findings suggest a number of improvements could be made to the program, such as including family members, and consideration being given to its routine early inclusion in diabetes management, ideally in primary care.

Lipid-lowering therapy use and achievement of cholesterol targets in an Australian diabetes clinic.

We documented temporal changes in the use of lipid-lowering medications and achievement of cholesterol targets in an Australian diabetes clinic. The number of patients using lipid-lowering therapy for primary or secondary cardiovascular prevention increased from 6 to 69% between 1993-1995 and 2014-2016, which corresponded to a decrease in low-density lipoprotein cholesterol levels from 3.7 to 2.4 mmol/L (P < 0.01).

Suboptimal behaviour and knowledge regarding overnight glycaemia in adults with type 1 diabetes is common.

BACKGROUND: In people with type 1 diabetes (T1D), nocturnal hypoglycaemia (NH) can be slept through and can cause seizures, arrhythmias and death. Hypoglycaemia avoidance can induce hyperglycaemia and ketosis. Patient behaviour impacts clinical outcomes and may be changed by education. AIM: To develop and utilise a survey to evaluate patient self-management of overnight glycaemia in adults with T1D. METHODS: Adults with T1D attending two Australian tertiary referral diabetes clinics completed a survey about their diabetes self-management and glycaemic control, including responses to hypothetical pre-bed blood glucose (BG) levels (4-20 mmol/L). Statistical analyses included t-tests, Chi square tests and ANOVA with significance considered at P < 0.05. RESULTS: There were 205 participants (103 females), with a mean (SD) age of 41 (17) years, T1D duration of 20 (16) years, HbA1c of 7.8(1.4)%, (61.3(8.2) mmol/mol), 38% on insulin pump therapy (CSII) and 36% with impaired hypoglycaemia awareness (IHA). Mean (SD) number of BG tests/day was 5.4 (2.7). Patients set higher BG target levels at bedtime and overnight: 7.5(1.4) and 7.1(1.3) mmol/L, respectively, compared to daytime (6.9(1.0); P < 0.0001 and P = 0.002 respectively). Only 36% of participants reported treating nocturnal hypoglycaemia (NH) with the recommended refined, then complex, carbohydrate. Only 28% of patients made safe choices in all bedtime BG scenarios, with higher rates for CSII users, P = 0.0005. Further education was desired by 32% of respondents, with higher rates in those with (44%) versus without IHA (25%), P = 0.006. CONCLUSIONS: Many adults with T1D have suboptimal knowledge and behaviour regarding overnight BG self-management. A survey, piloted herein, may facilitate the identification of patients who could benefit from further education.

Insulin pump basal adjustment for exercise in type 1 diabetes: a randomised crossover study.

AIMS/HYPOTHESIS: The aim of this study was to investigate the effects of exercise, vs rest, on circulating insulin and glucose, following pre-exercise insulin pump basal rate reduction. METHODS: This was an open-label, two-stage randomised crossover study of 14 adults (seven women, seven men) with type 1 diabetes established on insulin pump therapy. In each stage, participants fasted and insulin delivery was halved following a single insulin basal rate overnight. Exercise (30 min moderate-intensity stationary bicycle exercise, starting 60 min post-basal reduction) and rest stages were undertaken in random order at a university hospital. Randomisation was computer-generated, and allocation concealed via sequentially numbered sealed opaque envelopes. Venous blood was collected at 15 min intervals from 60 min pre- until 210 min post-basal rate reduction. Changes in plasma free insulin (the primary outcome), and changes in plasma glucose, with exercise were compared with changes when resting. Outcomes were assessed blinded to group assignment. RESULTS: Following basal rate reduction when rested, mean (± SE) free insulin decreased by 4.9 ± 2.9%, 16.2 ± 2.6% and 18.6 ± 3.2% at 1, 2 and 3 h, respectively (p < 0.05 after 75 min). With exercise, relative to rest, mean free insulin increased by 6 ± 2 pmol/l after 15 min and 5 ± 2 pmol/l after 30 min (p < 0.001), then declined post-exercise (p < 0.001). Three participants (mean baseline glucose 5.0 ± 0.1 mmol/l) required glucose supplementation to prevent or treat exercise-related hypoglycaemia. In the other 11 participants (mean baseline glucose 8.4 ± 0.5 mmol/l), glucose increased by 0.8 ± 0.3 mmol/l with exercise (p = 0.028). CONCLUSIONS/INTERPRETATION: Halving the basal insulin rate 1 h prior to exercise did not significantly reduce circulating free insulin by exercise commencement. Exercise itself transiently increased insulin levels. In participants with low-normal glucose pre-exercise, hypoglycaemia was not prevented by insulin basal rate reduction alone. Greater insulin basal rate reduction and supplemental carbohydrate may be required to prevent exercise-induced hypoglycaemia. TRIAL REGISTRATION: ANZCTR.org.au ACTRN12613000581763 FUNDING: Australian Diabetes Society, Hugh DT Williamson Foundation, Lynne Quayle Charitable Trust Fund.

Assessment of the relationship between hypoglycaemia awareness and autonomic function following islet cell/pancreas transplantation.

BACKGROUND: This study assesses the autonomic function of patients who have regained awareness of hypoglycaemia following islet cell or whole pancreas transplant. METHODS: Five patients with type 1 diabetes and either islet cell (four patients) or whole pancreas (one patient) transplant were assessed. These patients were age-matched and gender-matched to five patients with type 1 diabetes without transplant and preserved hypoglycaemia awareness and five healthy control participants without diabetes. All participants underwent (i) a battery of five cardiovascular autonomic function tests, (ii) quantitative sudomotor axonal reflex testing, and (iii) sympathetic skin response testing. RESULTS: Total recorded hypoglycaemia episodes per month fell from 76 pre-transplant to 13 at 0- to 3-month post-transplant (83% reduction). The percentage of hypoglycaemia episodes that patients were unaware of decreased from 97 to 69% at 0-3 months (p < 0.001, Fisher's exact test) and to 20% after 12 months (p < 0.0001, Fisher's exact test). This amelioration was maintained at the time of testing (mean time: 4.1 years later, range: 2-6 years). Presence of significant autonomic neuropathy was seen in all five transplanted patients (at least 2/3 above modalities abnormal) but in only one of the patients with diabetes without transplantation. CONCLUSIONS: The long-term maintenance of hypoglycaemia awareness that returns after islet cell/pancreas transplantation in patients with diabetes is not prevented by significant autonomic neuropathy and is better accounted for by other factors such as reversal of hypoglycaemia-associated autonomic failure.

The Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation does not improve the underestimation of Glomerular Filtration Rate (GFR) in people with diabetes and preserved renal function.

BACKGROUND: Our hypothesis was that both the Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) and Modification of Diet in Renal Disease (MDRD) equations would underestimate directly measured GFR (mGFR) to a similar extent in people with diabetes and preserved renal function. METHODS: In a cross-sectional study, bias (eGFR - mGFR) was compared for the CKD-EPI and MDRD equations, after stratification for mGFR levels. We also examined the ability of the CKD-EPI compared with the MDRD equation to correctly classify subjects to various CKD stages. In a longitudinal study of subjects with an early decline in GFR i.e., initial mGFR > 60 ml/min/1.73 m(2) and rate of decline in GFR (ΔmGFR) > 3.3 ml/min/1.73 m(2) per year, ΔmGFR (based on initial and final values) was compared with ΔeGFR by the CKD-EPI and MDRD equations over a mean of 9 years. RESULTS: In the cross-sectional study, mGFR for the whole group was 80 ± 2.2 ml/min/1.73 m(2) (n = 199, 75 % type 2 diabetes). For subjects with mGFR >90 ml/min/1.73 m(2) (mGFR: 112 ± 2.0, n = 76), both equations significantly underestimated mGFR to a similar extent: bias for CKD-EPI: -12 ± 1.4 ml/min/1.73 m(2) (p < 0.001) and for MDRD: -11 ± 2.1 ml/min/1.73 m(2) (p < 0.001). Using the CKD-EPI compared with the MDRD equation did not improve the number of subjects that were correctly classified to a CKD-stage. No biochemical or clinical patient characteristics were identified to account for the under estimation of mGFR values in the normal to high range by the CKD-EPI equation. In the longitudinal study (n = 30, 66 % type 1 diabetes), initial and final mGFR values were 102.8 ± 6 and 54.6 ± 6.0 ml/min/1.73 m(2), respectively. Mean ΔGFR (ml/min/1.73 m(2) per year) was 6.0 by mGFR compared with only 3.0 by MDRD and 3.2 by CKD-EPI (both p < 0.05 vs mGFR) CONCLUSIONS: Both the CKD-EPI and MDRD equations underestimate reference GFR values > 90 ml/min/1.73 m(2) as well as an early decline in GFR to a similar extent in people with diabetes. There is scope to improve methods for estimating an early decline in GFR.

Using the Scanning Fluid Dynamic Gauging Device to Understand the Cleaning of Baked Lard Soiling Layers.

Extended or repeated heating of food fats promotes polymerisation reactions that produce difficult-to-remove soil layers. Cleaning of these baked-on/burnt-on fat deposits was investigated using model layers generated by baking lard on 316 stainless steel discs. Rigorous characterisation of the layer material was difficult, as it was insoluble in most solvents. Cleaning was studied using the scanning fluid dynamic gauging technique developed by Gordon et al. (Meas Sci Technol 21:85-103, 2010), which provides non-contact in situ measurement of layer thickness at several sites on a sample in real time. Tests at 50 [Formula: see text]C with alkali (sodium hydroxide, pH 10.4-11) and three surfactant solutions indicated two removal mechanisms, related to the (1) roll-up and (2) dispersion mechanisms reported for oily oils, namely (1) penetration of solvent at the soil-liquid interface, resulting in detachment of the soil layer as a coherent film, observed with linear alkylbenzene sulfonic acid (LAS) and Triton X-100 and aqueous sodium hydroxide at pH 10.4-11; and (2) the breakdown promoted by the agent penetrating through the layer, observed with cetyl trimethyl ammonium bromide (CTAB), in which CTAB antagonised the cleaning action of LAS.

The high burden of inpatient diabetes mellitus: the Melbourne Public Hospitals Diabetes Inpatient Audit.

OBJECTIVE: To determine the prevalence of diabetes in inpatients in Melbourne hospitals. DESIGN: Point prevalence survey of all inpatients in each hospital on a single day between 30 November 2010 and 22 November 2012. SETTING: 11 hospitals in metropolitan Melbourne including community, secondary and tertiary hospitals and one aged care and rehabilitation centre. PARTICIPANTS: 2308 adult inpatients in all wards apart from intensive care, emergency, obstetrics and psychiatry. MAIN OUTCOME MEASURES: Point prevalence of self-reported diabetes, details of current medication, self-reported frequency of complications. RESULTS: Diabetes status was obtained in 2273 of 2308 inpatients (98.5%). Of these, 562 (24.7%) had diabetes (95% CI, 22.9%-26.5%). Diabetes prevalence ranged from 15.7% to 35.1% in different hospitals (P < 0.001). Patients with diabetes were older, heavier and more likely to be taking lipid-lowering, antihypertensive and blood-thinning medications. Of 388 patients with complete medication information, 270 (69.6%) were taking oral hypoglycaemic agents alone or in combination with insulin, 158 (40.7%) were treated with insulin (67 [17.3%] with insulin alone) and 51 (13.1%) were not taking medication for diabetes. The frequency of diabetes complications was very high: 207/290 (71.4%) for any microvascular complication, 275/527 (52.2%) for any macrovascular complication and 227/276 (82.2%) for any complication. CONCLUSION: The high burden of diabetes in Melbourne hospital inpatients has major implications for patient health and health care expenditure. Optimising care of these high-risk patients has the potential to decrease inpatient morbidity and length of stay as well as preventing or delaying future complications. A formal Australian national audit of inpatient diabetes would determine its true prevalence and consequences, allowing rational planning to deal with shortcomings in its management.

An exploratory trial of insulin initiation and titration among patients with type 2 diabetes in the primary care setting with retrospective continuous glucose monitoring as an adjunct: INITIATION study protocol.

BACKGROUND: Insulin initiation and titration in primary care is necessary to respond to the growing epidemic of type 2 diabetes (T2D). The INITIATION study aims to evaluate the impact of implementing a new model of care with Primary Care Physician and Practice Nurse (PN) teams supported by a Credentialed Diabetes Educator-Registered Nurse (CDE-RN) and endocrinologist in initiating and titrating basal and prandial insulin for T2D patients in the Australian healthcare system over 24 weeks. This study also explores the feasibility and efficacy of retrospective continuous glucose monitoring (r-CGM) in comparison with self-monitoring of blood glucose (SMBG) among people with T2D in primary care. METHODS/DESIGN: The study employs a before and after design with a nested exploratory trial of SMBG and r-CGM. A total of 102 insulin naïve T2D patients with a glycated haemoglobin (HbA1c) level of >7.5% in the previous 6 months while treated with maximal oral therapy will be recruited and screened from 22 primary care practices in Melbourne, Australia. All patients will be commenced on a basal insulin regimen following randomization into one of the two blood glucose monitoring arms, with intensification to a "basal plus" regimen if required. The outcomes of the new model of care will be benchmarked with data collected over the same period from a specialist setting in Melbourne, Australia. DISCUSSION: This article describes the study protocol and insulin treatment algorithm employed in the first study to explore r-CGM use among T2D in primary care. Findings from the INITIATION study will inform development of a larger randomized controlled trial. TRIAL REGISTRATION: ACTRN12610000797077.

New treatments for type 2 diabetes: cardiovascular protection beyond glucose lowering?

The health burden of type 2 diabetes mellitus (T2DM) is increasing worldwide, with a substantial portion of this burden being due to the development of cardiovascular (CV) disease. Multiple individual randomised clinical trials of intensive versus conventional glucose control, based on the use of traditional oral hypoglycaemic agents, have failed to convincingly show that intensive glucose control significantly reduces CV disease outcomes. In recent times, two new approaches to lowering glucose levels have become available. One targets the "incretin effect" which involves the modulation of peptide hormones that normally regulate glucose levels when nutrients are given orally. The other approach is based on inhibiting the sodium-glucose co-transporter 2 (SGLT-2) in the tubules of the kidney to promote glycosuria. Incretin-based therapies, especially glucagon-like peptide-1 receptor analogues, reduce glucose levels, with a low risk of hypoglycaemia, by increasing insulin secretion, inhibiting glucagon release and increasing satiety. Clinical and experimental studies have also shown favourable effects on CV disease risk factors such as dyslipidaemia, blood pressure, and improvements in endothelial function and cardiac contractility. Similarly, SGLT-2 inhibitors reduce glucose levels with a low risk for hypoglycaemia and have positive effects on multiple CV disease risk factors. Whether the beneficial effects of these new glucose lowering approaches on surrogate markers of CV disease risk translates to an improvement in CV events remains unknown. Several CV outcome trials are currently being performed to show that at a minimum, these novel glucose lowering agents are safe, but also have positive CV benefits.

Interactive calculator to estimate insulin sensitivity in type 1 diabetes.

The gold standard for measuring insulin sensitivity (IS) is the hyperinsulinemic-euglycemic clamp, a time, costly, and labor-intensive research tool. A low insulin sensitivity is associated with a complication-risk in type 1 diabetes. Various formulae using clinical data have been developed and correlated with measured IS in type 1 diabetes. We consolidated multiple formulae into an online calculator (bit.ly/estimated-GDR), enabling comparison of IS and its probability of IS <4.45 mg/kg/min (low) or >6.50 mg/kg/min (high), as measured in a validation set of clamps in 104 adults with type 1 diabetes. Insulin sensitivity calculations using different formulae varied significantly, with correlations (R2) ranging 0.005-0.87 with agreement in detecting low and high glucose disposal rates in the range 49-93% and 89-100%, respectively. We demonstrate that although the calculated IS varies between formulae, their interpretation remains consistent. Our free online calculator offers a user-friendly tool for individual IS calculations and also offers efficient batch processing of data for research.

Hybrid Closed Loop in Adults With Type 1 Diabetes and Severely Impaired Hypoglycemia Awareness.

BACKGROUND: Benefits of hybrid closed-loop (HCL) systems in a high-risk group with type 1 diabetes and impaired awareness of hypoglycemia (IAH) have not been well-explored. METHODS: Adults with Edmonton HYPO scores ≥1047 were randomized to 26-weeks HCL (MiniMed™ 670G) vs standard therapy (multiple daily injections or insulin pump) without continuous glucose monitoring (CGM) (control). Primary outcome was percentage CGM time-in-range (TIR; 70-180 mg/dL) at 23 to 26 weeks post-randomization. Major secondary endpoints included magnitude of change in counter-regulatory hormones and autonomic symptom responses to hypoglycemia at 26-weeks post-randomization. A post hoc analysis evaluated glycemia risk index (GRI) comparing HCL with control groups at 26 weeks post-randomization. RESULTS: Nine participants (median [interquartile range (IQR)] age 51 [41, 59] years; 44% male; enrolment HYPO score 1183 [1058, 1308]; Clarke score 6 [6, 6]; n = 5 [HCL]; n = 4 [control]) completed the study. Time-in-range was higher using HCL vs control (70% [68, 74%] vs 48% [44, 50%], P = .014). Time <70 mg/dL did not differ (HCL 3.8% [2.7, 3.9] vs control 6.5% [4.3, 8.6], P = .14) although hypoglycemia episode duration was shorter (30 vs 50 minutes, P < .001) with HCL. Glycemia risk index was lower with HCL vs control (38.1 [30.0, 39.2] vs 70.8 [58.5, 72.4], P = .014). Following 6 months of HCL use, greater dopamine (24.0 [12.3, 27.6] vs -18.5 [-36.5, -4.8], P = .014), and growth hormone (6.3 [4.6, 16.8] vs 0.5 [-0.8, 3.0], P = .050) responses to hypoglycemia were observed. CONCLUSIONS: Six months of HCL use in high-risk adults with severe IAH increased glucose TIR and improved GRI without increased hypoglycemia, and partially restored counter-regulatory responses. CLINICAL TRIAL REGISTRATION: ACTRN12617000520336.

Driving-Related Glucose Patterns Among Older Adults with Type 1 Diabetes.

Older adults with type 1 diabetes may face challenges driving safely. Glucose "above-5-to-drive" is often recommended for insulin-treated diabetes to minimize hypoglycemia while driving. However, the effectiveness of this recommendation among older adults has not been evaluated. Older drivers with type 1 diabetes were assessed while using sensor-augmented insulin pumps during a 2-week clinical trial run-in. Twenty-three drivers (median age 69 years [interquartile range; IQR 65-72]; diabetes duration 37 years [20-45]) undertook 618 trips (duration 10 min [5-21]). Most trips (n = 535; 87%) were <30 min duration; 9 trips (1.5%) exceeded 90 min and 3 trips (0.5%) exceeded 120 min. Pre-trip continuous glucose monitoring (CGM) was >5.0 mmol/L for 577 trips (93%) and none of these had CGM <3.9 mmol/L during driving (including 8 trips >90 min and 3 trips >120 min). During 41 trips with pre-trip CGM ≤5.0 mmol/L, 11 trips had CGM <3.9 mmol/L. Seventy-one CGM alerts occurred during 60 trips (10%), of which 54 of 71 alerts (76%) were unrelated to hypoglycemia. Our findings support a glucose "above-5-to-drive" recommendation to avoid CGM-detected hypoglycemia among older drivers, including for prolonged drives, and highlight the importance of active CGM low-glucose alerts to prevent hypoglycemia during driving. Driving-related CGM usability and alert functionality warrant investigation. Clinical trial ACTRN1261900515190.

The Mediterranean diet improves hepatic steatosis and insulin sensitivity in individuals with non-alcoholic fatty liver disease.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) affects up to 30% of the population and signifies increased risk of liver fibrosis and cirrhosis, type 2 diabetes, and cardiovascular disease. Therapies are limited. Weight loss is of benefit but is difficult to maintain. We aimed at examining the effect of the Mediterranean diet (MD), a diet high in monounsaturated fatty acids, on steatosis and insulin sensitivity, using gold standard techniques. METHODS: Twelve non-diabetic subjects (6 Females/6 Males) with biopsy-proven NAFLD were recruited for a randomised, cross-over 6-week dietary intervention study. All subjects undertook both the MD and a control diet, a low fat-high carbohydrate diet (LF/HCD), in random order with a 6-week wash-out period in- between. Insulin sensitivity was determined with a 3-h hyperinsulinemic-euglycemic clamp study and hepatic steatosis was assessed with localized magnetic resonance (1)H spectroscopy ((1)H-MRS). RESULTS: At baseline, subjects were abdominally obese with elevated fasting concentrations of glucose, insulin, triglycerides, ALT, and GGT. Insulin sensitivity at baseline was low (M=2.7 ± 1.0 mg/kg/min(-1)). Mean weight loss was not different between the two diets (p=0.22). There was a significant relative reduction in hepatic steatosis after the MD compared with the LF/HCD: 39 ± 4% versus 7 ± 3%, as measured by (1)H-MRS (p=0.012). Insulin sensitivity improved with the MD, whereas after the LF/HCD there was no change (p=0.03 between diets). CONCLUSIONS: Even without weight loss, MD reduces liver steatosis and improves insulin sensitivity in an insulin-resistant population with NAFLD, compared to current dietary advice. This diet should be further investigated in subjects with NAFLD.