Observational Study of the Association of First Insulin Type in Uncontrolled Type 2 Diabetes with Macrovascular and Microvascular Disease

Gillian C Hall,Dawn Carroll,Alex D Mcmahon,Philip D Home,Xin-Liang Ma

doi:10.1371/journal.pone.0049908

Gillian C Hall, Dawn Carroll + Show 3 more

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https://doi.org/10.1371/journal.pone.0049908

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Abstract

AimsTo compare the risk of vascular disease, HbA1c and weight change, between first prescribed insulins in people with type 2 diabetes.MethodsPeople included in THIN United Kingdom primary care record database who began insulin (2000–2007) after poor control on oral glucose-lowering agents (OGLD) were grouped by the number of OGLDs in their treatment regimen immediately before starting insulin (n = 3,485). Within OGLD group, Cox regression compared macrovascular (all-cause mortality, myocardial infarction, acute coronary syndrome and stroke) and microvascular disease (peripheral neuropathy, nephropathy, and retinopathy) between insulin type (basal, pre-mix or Neutral Protamine Hagedorn, NPH) while ANCOVAs compared haemoglobin A1c (HbA1c) and weight change.ResultsMean follow-up was 3.6 years. Rates of incident macrovascular events were similar when basal insulin was compared to pre-mix or NPH, adjusted hazard ratio versus basal: pre-mix 1.08 (95% CI 0.73, 1.59); NPH 1.00 (0.63, 1.58) after two OGLDs, and pre-mix 0.97 (0.46, 2.02); NPH 0.77 (0.32, 1.86) after three OGLDs. An increased risk of microvascular disease in NPH versus basal after 3 OGLDs, adjusted hazard ratio1.87 (1.04, 3.36), was not seen after two agents or in comparisons of basal and pre-mix. At one year, after two OGLDs, weight increase was less with basal compared with pre-mix. After three OGLDs, mean HbA1c had reduced less in basal versus pre-mix or NPH at 6–8 and at 9–11 months, and versus pre-mix at 12–14 months.ConclusionWe found no difference in the risk of macrovascular events between first insulins in the medium term when started during poor glycaemia control. The increased risk of microvascular events with NPH warrants further study. In certain groups, first use of basal insulin was associated with less gain in weight and decrease in HbA1c compared to other insulins.

Highlights

A short-term aim of type 2 diabetes management is good glycaemic control with a longer-term objective of reducing complications
Source Population All data came from The Health Information Network (THIN), an observational database containing information collected in computerized primary care practices throughout the United Kingdom (UK) [8]
Baseline therapies were similar across insulin types with the majority of people on two baseline therapies being prescribed metformin and a sulfonylurea with a thiazolidinedione added as the third agent (Table 2)

Summary

Introduction

A short-term aim of type 2 diabetes management is good glycaemic control with a longer-term objective of reducing complications. A steady decline in islet b-cell function usually results in progressive hyperglycaemia so a stepwise escalation in the number of OGLDs prescribed is frequently required to maintain glycaemic control. Many people require insulin to maintain glycaemic control as insulin secretion decreases [2]. The choice when beginning insulin treatment is usually between human NPH insulin (NPH) injected once or twice daily, a long-acting basal insulin analogue (basal) or a pre-mix preparation. Current United Kingdom (UK) National Institute for Health and Clinical Excellence guidance recommends beginning with NPH but to consider long-acting analogues or pre-mixed insulin formulations under specified circumstances [3]

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