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Published in: Diabetologia 3/2018

Open Access 01-03-2018 | Article

Rates of glycaemic deterioration in a real-world population with type 2 diabetes

Authors: Louise A. Donnelly, Kaixin Zhou, Alex S. F. Doney, Chris Jennison, Paul W. Franks, Ewan R. Pearson

Published in: Diabetologia | Issue 3/2018

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Abstract

Aims/hypothesis

There is considerable variability in how diabetes progresses after diagnosis. Progression modelling has largely focused on ‘time to failure’ methods, yet determining a ‘coefficient of failure’ has many advantages. We derived a rate of glycaemic deterioration in type 2 diabetes, using a large real-world cohort, and aimed to investigate the clinical, biochemical, pharmacological and immunological variables associated with fast and slow rates of glycaemic deterioration.

Methods

An observational cohort study was performed using the electronic medical records from participants in the Genetics of Diabetes Audit and Research in Tayside Study (GoDARTS). A model was derived based on an individual’s observed HbA1c measures from the first eligible HbA1c after the diagnosis of diabetes through to the study end (defined as insulin initiation, death, leaving the area or end of follow-up). Each HbA1c measure was time-dependently adjusted for the effects of non-insulin glucose-lowering drugs, changes in BMI and corticosteroid use. GAD antibody (GADA) positivity was defined as GAD titres above the 97.5th centile of the population distribution.

Results

The mean (95% CI) glycaemic deterioration for type 2 diabetes and GADA-positive individuals was 1.4 (1.3, 1.4) and 2.8 (2.4, 3.3) mmol/mol HbA1c per year, respectively. A younger age of diagnosis, lower HDL-cholesterol concentration, higher BMI and earlier calendar year of diabetes diagnosis were independently associated with higher rates of glycaemic deterioration in individuals with type 2 diabetes. The rate of deterioration in those diagnosed at over 70 years of age was very low, with 66% having a rate of deterioration of less than 1.1 mmol/mol HbA1c per year, and only 1.5% progressing more rapidly than 4.4 mmol/mol HbA1c per year.

Conclusions/interpretation

We have developed a novel approach for modelling the progression of diabetes in observational data across multiple drug combinations. This approach highlights how glycaemic deterioration in those diagnosed at over 70 years of age is minimal, supporting a stratified approach to diabetes management.
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Literature
1.
go back to reference Levy J, Atkinson AB, Bell PM, McCance DR, Hadden DR (1998) Beta-cell deterioration determines the onset and rate of progression of secondary dietary failure in type 2 diabetes mellitus: the 10-year follow-up of the Belfast Diet Study. Diabet Med 15:290–296CrossRefPubMed Levy J, Atkinson AB, Bell PM, McCance DR, Hadden DR (1998) Beta-cell deterioration determines the onset and rate of progression of secondary dietary failure in type 2 diabetes mellitus: the 10-year follow-up of the Belfast Diet Study. Diabet Med 15:290–296CrossRefPubMed
2.
go back to reference U.K. Prospective Diabetes Study Group (1995) U.K. prospective diabetes study 16. Overview of 6 years' therapy of type II diabetes: a progressive disease. Diabetes 44:1249–1258 U.K. Prospective Diabetes Study Group (1995) U.K. prospective diabetes study 16. Overview of 6 years' therapy of type II diabetes: a progressive disease. Diabetes 44:1249–1258
3.
go back to reference Turner R, Stratton I, Horton V et al (1997) UKPDS 25: autoantibodies to islet-cell cytoplasm and glutamic acid decarboxylase for prediction of insulin requirement in type 2 diabetes. UK Prospective Diabetes Study Group. Lancet 350: 1288–1293 Turner R, Stratton I, Horton V et al (1997) UKPDS 25: autoantibodies to islet-cell cytoplasm and glutamic acid decarboxylase for prediction of insulin requirement in type 2 diabetes. UK Prospective Diabetes Study Group. Lancet 350: 1288–1293
4.
go back to reference Matthews DR, Cull CA, Stratton IM, Holman RR, Turner RC (1998) UKPDS 26: sulphonylurea failure in non-insulin-dependent diabetic patients over six years. UK Prospective Diabetes Study (UKPDS) Group. Diabet Med 15: 297–303 Matthews DR, Cull CA, Stratton IM, Holman RR, Turner RC (1998) UKPDS 26: sulphonylurea failure in non-insulin-dependent diabetic patients over six years. UK Prospective Diabetes Study (UKPDS) Group. Diabet Med 15: 297–303
5.
go back to reference Ringborg A, Lindgren P, Yin DD, Martinell M, Stalhammar J (2010) Time to insulin treatment and factors associated with insulin prescription in Swedish patients with type 2 diabetes. Diabetes Metab 36:198–203CrossRefPubMed Ringborg A, Lindgren P, Yin DD, Martinell M, Stalhammar J (2010) Time to insulin treatment and factors associated with insulin prescription in Swedish patients with type 2 diabetes. Diabetes Metab 36:198–203CrossRefPubMed
6.
go back to reference Zhou K, Donnelly LA, Morris AD et al (2014) Clinical and genetic determinants of progression of type 2 diabetes: a DIRECT study. Diabetes Care 37:718–724CrossRefPubMed Zhou K, Donnelly LA, Morris AD et al (2014) Clinical and genetic determinants of progression of type 2 diabetes: a DIRECT study. Diabetes Care 37:718–724CrossRefPubMed
7.
go back to reference Cook MN, Girman CJ, Stein PP, Alexander CM, Holman RR (2005) Glycemic control continues to deteriorate after sulfonylureas are added to metformin among patients with type 2 diabetes. Diabetes Care 28:995–1000CrossRefPubMed Cook MN, Girman CJ, Stein PP, Alexander CM, Holman RR (2005) Glycemic control continues to deteriorate after sulfonylureas are added to metformin among patients with type 2 diabetes. Diabetes Care 28:995–1000CrossRefPubMed
8.
go back to reference Pani LN, Nathan DM, Grant RW (2008) Clinical predictors of disease progression and medication initiation in untreated patients with type 2 diabetes and A1C less than 7%. Diabetes Care 31:386–390CrossRefPubMed Pani LN, Nathan DM, Grant RW (2008) Clinical predictors of disease progression and medication initiation in untreated patients with type 2 diabetes and A1C less than 7%. Diabetes Care 31:386–390CrossRefPubMed
9.
go back to reference Waldman B, Jenkins AJ, Davis TM et al (2014) HDL-C and HDL-C/ApoA-I predict long-term progression of glycemia in established type 2 diabetes. Diabetes Care 37:2351–2358CrossRefPubMed Waldman B, Jenkins AJ, Davis TM et al (2014) HDL-C and HDL-C/ApoA-I predict long-term progression of glycemia in established type 2 diabetes. Diabetes Care 37:2351–2358CrossRefPubMed
10.
go back to reference Wallace TM, Matthews DR (2002) Coefficient of failure: a methodology for examining longitudinal beta-cell function in type 2 diabetes. Diabet Med 19:465–469CrossRefPubMed Wallace TM, Matthews DR (2002) Coefficient of failure: a methodology for examining longitudinal beta-cell function in type 2 diabetes. Diabet Med 19:465–469CrossRefPubMed
11.
go back to reference Kahn SE, Haffner SM, Heise MA et al (2006) Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med 355:2427–2443CrossRefPubMed Kahn SE, Haffner SM, Heise MA et al (2006) Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med 355:2427–2443CrossRefPubMed
12.
go back to reference Doney AS, Fischer B, Leese G, Morris AD, Palmer CN (2004) Cardiovascular risk in type 2 diabetes is associated with variation at the PPARG locus: a Go-DARTS study. Arterioscler Thromb Vasc Biol 24:2403–2407CrossRefPubMed Doney AS, Fischer B, Leese G, Morris AD, Palmer CN (2004) Cardiovascular risk in type 2 diabetes is associated with variation at the PPARG locus: a Go-DARTS study. Arterioscler Thromb Vasc Biol 24:2403–2407CrossRefPubMed
13.
go back to reference Doney AS, Lee S, Leese GP, Morris AD, Palmer CN (2005) Increased cardiovascular morbidity and mortality in type 2 diabetes is associated with the glutathione S transferase theta-null genotype: a Go-DARTS study. Circulation 111:2927–2934CrossRefPubMed Doney AS, Lee S, Leese GP, Morris AD, Palmer CN (2005) Increased cardiovascular morbidity and mortality in type 2 diabetes is associated with the glutathione S transferase theta-null genotype: a Go-DARTS study. Circulation 111:2927–2934CrossRefPubMed
14.
go back to reference Hirst JA, Farmer AJ, Ali R, Roberts NW, Stevens RJ (2012) Quantifying the effect of metformin treatment and dose on glycemic control. Diabetes Care 35:446–454CrossRefPubMedPubMedCentral Hirst JA, Farmer AJ, Ali R, Roberts NW, Stevens RJ (2012) Quantifying the effect of metformin treatment and dose on glycemic control. Diabetes Care 35:446–454CrossRefPubMedPubMedCentral
15.
Metadata
Title
Rates of glycaemic deterioration in a real-world population with type 2 diabetes
Authors
Louise A. Donnelly
Kaixin Zhou
Alex S. F. Doney
Chris Jennison
Paul W. Franks
Ewan R. Pearson
Publication date
01-03-2018
Publisher
Springer Berlin Heidelberg
Published in
Diabetologia / Issue 3/2018
Print ISSN: 0012-186X
Electronic ISSN: 1432-0428
DOI
https://doi.org/10.1007/s00125-017-4519-5

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