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Introduction: If a person is in diabetes remission, even if only for a short time, this reduces the risk of later diabetes complications and lowers healthcare costs. A recent study shows that long-term remission of type 2 diabetes can be achieved through calorie restriction using total diet replacement. However, this intervention involves support through face-to-face meetings every 2 to 4 weeks over a 2-year period, which is not feasible in routine care with limited resources. Therefore, we have developed an eHealth programme to help patients achieve diabetes remission through calorie restriction in a cost-effective manner. Our primary hypothesis is that an eHealth programme will be non-inferior to face-to-face meetings in helping patients with type 2 diabetes achieve remission through caloric restriction. Our second hypothesis is that eHealth support will be more cost-effective than face-to-face support.

Methods and analysis: The eHealth DIabetes remission Trial is a multicentre, two-arm, non-inferiority, open-label, randomised controlled parallel group trial with blinded endpoint assessment conducted at two centres in Sweden. The study duration is 2 years. People with type 2 diabetes (≤6 years duration) use total diet replacement (approximately 900 kcal/day) with the aim of losing 15 kg and achieving diabetes remission. Participants are randomly assigned to either the eHealth support group or the face-to-face support group. The treatment programme to achieve and maintain weight loss is the same in both groups, but the method of support differs between the groups. The primary outcome is haemoglobin A1c (HbA1c) after 1 year. The secondary outcome is HbA1c at 6 months and 2 years. Other important secondary outcomes are diabetes remission rate, body weight and cost-effectiveness. The latter is assessed using the incremental cost per quality-adjusted life-years gained.

Ethics and dissemination: The study was approved by the Swedish Ethical Review Authority (Dnr 2022-02242-01, 2023-03707-02). The results will be published in peer-reviewed scientific journals and discussed at national and international conferences and with patient organisations.

Introduction: In this systematic review, we investigated the diagnostic accuracy of surrogate measures of insulin secretion based on fasting samples and the oral glucose tolerance test (OGTT). The first phase of insulin secretion was calculated using two gold standard methods; the hyperglycemic clamp (HGC) test and intravenous glucose tolerance test (IVGTT).

Research design and methods: We conducted searches in the PubMed, Cochrane Central, and Web of Science databases, the last of which was conducted at the end of June 2021. Studies were included that measured first-phase insulin secretion in adults using both a gold-standard reference method (either HGC or IVGTT) and one or more surrogate measures from either fasting samples, OGTT or a meal-tolerance test. QUADAS-2, a revised tool for the quality assessment of diagnostic accuracy studies, was used for quality assessment. Random-effects meta-analyses were performed to examine the correlation between first-phase measured with gold standard and surrogate methods.

Results: A total of 33 articles, encompassing 5362 individuals with normal glucose tolerance, pre-diabetes or type 2 diabetes, were included in our systematic review. Homeostatic model assessment (HOMA)-beta and Insulinogenic Index 30 (IGI(30)) were the surrogate measures validated in the largest number of studies (17 and 13, respectively). HOMA-beta's pooled correlation to the reference methods was 0.48 (95% CI 0.40 to 0.56) The pooled correlation of IGI to the reference methods was 0.61 (95% CI 0.54 to 0.68). The surrogate measures with the highest correlation to the reference methods were Kadowaki (0.67 (95% CI 0.61 to 0.73)) and Stumvoll's first-phase secretion (0.65 (95% CI 0.58 to 0.71)), both calculated from an OGTT.

Conclusions: Surrogate measures from the first 30 min of an OGTT capture the first phase of insulin secretion and are a good choice for epidemiological studies. HOMA-beta has a moderate correlation to the reference methods but is not a measure of the first phase specifically.

INTRODUCTION: With pre-diabetes and diabetes increasingly recognized as heterogeneous conditions, assessment of beta-cell function is gaining clinical importance to identify disease subphenotypes. Our study aims to comprehensively validate all types of surrogate indices based on oral glucose tolerance test (OGTT) and fasting measurements in comparison with gold standard methods.

RESEARCH DESIGN AND METHODS: The hyperglycemic clamp extended with glucagon-like peptide 1 (GLP-1) infusion and intravenous glucose tolerance test (IVGTT), as well as OGTT, was performed in two well-phenotyped cohorts. The gold standard-derived indices were compared with surrogate insulin secretion markers, derived from fasting state and OGTT, using both Pearson's and Spearman's correlation coefficients. The insulin-based and C-peptide-based indices were analyzed separately in different groups of glucose tolerance and the entire cohorts.

RESULTS: The highest correlation coefficients were found for area under curve (AUC) (I_0-30)/AUC (G_0-30), I₃₀/G₃₀, first-phase Stumvoll and Kadowaki model. These indices have high correlation coefficients with measures obtained from both insulin and C-peptide levels from IVGTT and hyperglycemic clamp. AUC (I_0-120)/AUC (G_0-120), BIGTT-AIR_0-60-120, I₃₀/G₃₀, first-phase Stumvoll and AUC (I_0-30)/AUC (G_0-30) demonstrated the strongest association with incretin-stimulated insulin response.

CONCLUSIONS: We have identified glucose-stimulated and GLP-1-stimulated insulin secretion indices, derived from OGTT and fasting state, that have the strongest correlation with gold standard measures and could be potentially used in future researches and clinical practice.