Time to insulin initiation and long-term effects of initiating insulin in people with type 2 diabetes mellitus: the Hoorn Diabetes Care System Cohort Study

Abstract

Objective: The aim of this study was to assess the time to insulin initiation in type 2 diabetes mellitus (T2DM) patients treated with oral glucose-lowering agents and to determine the baseline characteristics associated with time to insulin initiation. This was evaluated in T2DM patients with HbA1c levels consistently R7.0% during total follow up and in those with fluctuating HbA1c levels around 7.0%. Design and methods: Prospective, observational study was performed, comprising 2418 persons with T2DM aged R40 years who entered the Diabetes Care System between 1998 and 2012 with a minimum follow up of at least 3 years, following the first HbA1c level R7.0%. Cox regression analyses were performed to assess the determinants of time to insulin initiation. Data related to long-term effects of insulin initiation were studied at baseline and at the end of follow up using descriptive summary statistics. Results: Two-thirds of the patients initiated insulin during follow up. The time to insulin varied from 1.2 years (range 0.3-3.1) in patients with HbA1c levels consistently R7.0% to 5.4 years (range 3.0-7.5) in patients with fluctuating HbA1c levels around 7.0%. Longer diabetes duration (hazard ratio (HR) 1.04 95% CI 1.03-1.05) and lower age (HR 1.00 95% CI 0.99-1.00) at baseline were associated with a shorter time to initiation. More insulin initiators had retinopathy compared with patients that remained on oral glucose-lowering agents during follow up. Conclusion: The time to insulin initiation was short, and most of the patients with HbA1c levels consistently R7.0% were initiating insulin. Longer diabetes duration and younger age shortened the time to insulin.

The impact of phenotype, ethnicity and genotype on progression of type 2 diabetes mellitus

“…From the 61 included articles, 56 studies assessed the phenotypic factors affecting diabetes progression, while only four studies investigated genotypic determinants of diabetes progression and one study assessed both phenotypic and genotypic factors . Before 2000, there were only four studies published and between 2000 and 2010; there were 20 studies published, with the remaining 37 studies published after 2010.…”

“…Before 2000, there were only four studies published and between 2000 and 2010; there were 20 studies published, with the remaining 37 studies published after 2010. The 61 studies were comprised of 35 retrospective cohort studies, 19 prospective cohort studies, three cross‐sectional studies, three case‐control studies studies and one randomized controlled trial (RCT) . The sample size ranged from 50 to 366 955 individuals, and most of the studies were from developed countries with European, American and Australian populations.…”

“…A total of 27 studies established the association of younger age of diabetes onset with increased diabetes progression. Of these, 22 were retrospective, three were prospective, one was a RCT, and one was a cross‐sectional study …”

“…Analysis of the Look AHEAD trial data showed that younger age of diabetes diagnosis was associated with faster rate of insulin initiation, with an aHR 0.88 (95% CI 0.79‐0.98) per 10 year of age of diagnosis . In the prospective studies, two studies used time to insulin, and one used diet failure as the progression phenotype, with all three studies concluding that younger age of diagnosis was associated with faster progression …”

“…Eight studies examined the relationship between time to insulin and diabetes duration, of these six were retrospective and two were prospective cohort studies . Diabetes duration is defined as the time between diabetes diagnosis and entry into the study.…”