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

Anand Thakarakkattil Narayanan Nair, Louise A. Donnelly, Adem Y. Dawed, Sushrima Gan, Ranjit M. Anjana, Viswanathan Mohan, Colin Palmer, Ewan Pearson (Lead / Corresponding author)

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Abstract

Aim
To conduct a comprehensive review of studies of glycaemic deterioration in type 2 diabetes and identify the major factors influencing progression.

Methods
We conducted a systematic literature search with terms linked to type 2 diabetes progression. All the included studies were summarized based upon the factors associated with diabetes progression and how the diabetes progression was defined.

Results
Our search yielded 2785 articles; based on title, abstract and full‐text review, we included 61 studies in the review. We identified seven criteria for diabetes progression: ‘Initiation of insulin’, ‘Initiation of oral antidiabetic drug’, ‘treatment intensification’, ‘antidiabetic therapy failure’, ‘glycaemic deterioration’, ‘decline in beta‐cell function’ and ‘change in insulin dose’. The determinants of diabetes progression were grouped into phenotypic, ethnicity and genotypic factors. Younger age, poorer glycaemia and higher body mass index at diabetes diagnosis were the main phenotypic factors associated with rapid progression. The effect of genotypic factors on progression was assessed using polygenic risk scores (PRS); a PRS constructed from the genetic variants linked to insulin resistance was associated with rapid glycaemic deterioration. The evidence of impact of ethnicity on progression was inconclusive due to the small number of multi‐ethnic studies.

Conclusion
We have identified the major determinants of diabetes progression—younger age, higher BMI, higher HbA1c and genetic insulin resistance. The impact of ethnicity is uncertain; there is a clear need for more large‐scale studies of diabetes progression in different ethnic groups.
Original languageEnglish
Article numbere00108
Number of pages11
JournalEndocrinology, Diabetes & Metabolism
Early online date7 Jan 2020
DOIs
Publication statusE-pub ahead of print - 7 Jan 2020

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Hypoglycemic Agents
Type 2 Diabetes Mellitus
Insulin Resistance
Genotype
Insulin
Phenotype
Ethnic Groups
Body Mass Index
Therapeutics

Cite this

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title = "The impact of phenotype, ethnicity and genotype on progression of Type 2 diabetes mellitus",
abstract = "AimTo conduct a comprehensive review of studies of glycaemic deterioration in type 2 diabetes and identify the major factors influencing progression.MethodsWe conducted a systematic literature search with terms linked to type 2 diabetes progression. All the included studies were summarized based upon the factors associated with diabetes progression and how the diabetes progression was defined.ResultsOur search yielded 2785 articles; based on title, abstract and full‐text review, we included 61 studies in the review. We identified seven criteria for diabetes progression: ‘Initiation of insulin’, ‘Initiation of oral antidiabetic drug’, ‘treatment intensification’, ‘antidiabetic therapy failure’, ‘glycaemic deterioration’, ‘decline in beta‐cell function’ and ‘change in insulin dose’. The determinants of diabetes progression were grouped into phenotypic, ethnicity and genotypic factors. Younger age, poorer glycaemia and higher body mass index at diabetes diagnosis were the main phenotypic factors associated with rapid progression. The effect of genotypic factors on progression was assessed using polygenic risk scores (PRS); a PRS constructed from the genetic variants linked to insulin resistance was associated with rapid glycaemic deterioration. The evidence of impact of ethnicity on progression was inconclusive due to the small number of multi‐ethnic studies.ConclusionWe have identified the major determinants of diabetes progression—younger age, higher BMI, higher HbA1c and genetic insulin resistance. The impact of ethnicity is uncertain; there is a clear need for more large‐scale studies of diabetes progression in different ethnic groups.",
author = "{Thakarakkattil Narayanan Nair}, Anand and Donnelly, {Louise A.} and Dawed, {Adem Y.} and Sushrima Gan and Anjana, {Ranjit M.} and Viswanathan Mohan and Colin Palmer and Ewan Pearson",
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doi = "10.1002/edm2.108",
language = "English",

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T1 - The impact of phenotype, ethnicity and genotype on progression of Type 2 diabetes mellitus

AU - Thakarakkattil Narayanan Nair, Anand

AU - Donnelly, Louise A.

AU - Dawed, Adem Y.

AU - Gan, Sushrima

AU - Anjana, Ranjit M.

AU - Mohan, Viswanathan

AU - Palmer, Colin

AU - Pearson, Ewan

N1 - National Institute for Health Research

PY - 2020/1/7

Y1 - 2020/1/7

N2 - AimTo conduct a comprehensive review of studies of glycaemic deterioration in type 2 diabetes and identify the major factors influencing progression.MethodsWe conducted a systematic literature search with terms linked to type 2 diabetes progression. All the included studies were summarized based upon the factors associated with diabetes progression and how the diabetes progression was defined.ResultsOur search yielded 2785 articles; based on title, abstract and full‐text review, we included 61 studies in the review. We identified seven criteria for diabetes progression: ‘Initiation of insulin’, ‘Initiation of oral antidiabetic drug’, ‘treatment intensification’, ‘antidiabetic therapy failure’, ‘glycaemic deterioration’, ‘decline in beta‐cell function’ and ‘change in insulin dose’. The determinants of diabetes progression were grouped into phenotypic, ethnicity and genotypic factors. Younger age, poorer glycaemia and higher body mass index at diabetes diagnosis were the main phenotypic factors associated with rapid progression. The effect of genotypic factors on progression was assessed using polygenic risk scores (PRS); a PRS constructed from the genetic variants linked to insulin resistance was associated with rapid glycaemic deterioration. The evidence of impact of ethnicity on progression was inconclusive due to the small number of multi‐ethnic studies.ConclusionWe have identified the major determinants of diabetes progression—younger age, higher BMI, higher HbA1c and genetic insulin resistance. The impact of ethnicity is uncertain; there is a clear need for more large‐scale studies of diabetes progression in different ethnic groups.

AB - AimTo conduct a comprehensive review of studies of glycaemic deterioration in type 2 diabetes and identify the major factors influencing progression.MethodsWe conducted a systematic literature search with terms linked to type 2 diabetes progression. All the included studies were summarized based upon the factors associated with diabetes progression and how the diabetes progression was defined.ResultsOur search yielded 2785 articles; based on title, abstract and full‐text review, we included 61 studies in the review. We identified seven criteria for diabetes progression: ‘Initiation of insulin’, ‘Initiation of oral antidiabetic drug’, ‘treatment intensification’, ‘antidiabetic therapy failure’, ‘glycaemic deterioration’, ‘decline in beta‐cell function’ and ‘change in insulin dose’. The determinants of diabetes progression were grouped into phenotypic, ethnicity and genotypic factors. Younger age, poorer glycaemia and higher body mass index at diabetes diagnosis were the main phenotypic factors associated with rapid progression. The effect of genotypic factors on progression was assessed using polygenic risk scores (PRS); a PRS constructed from the genetic variants linked to insulin resistance was associated with rapid glycaemic deterioration. The evidence of impact of ethnicity on progression was inconclusive due to the small number of multi‐ethnic studies.ConclusionWe have identified the major determinants of diabetes progression—younger age, higher BMI, higher HbA1c and genetic insulin resistance. The impact of ethnicity is uncertain; there is a clear need for more large‐scale studies of diabetes progression in different ethnic groups.

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