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Highlighting the Role of Obesity and Insulin Resistance in Type 1 Diabetes and Its Associated Cardiometabolic Complications

  • The Obesity Epidemic: Causes and Consequences (A Cameron and K Backholer, Section Editors)
  • Published:
Current Obesity Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

This narrative review appraises research data on the potentially harmful effect of obesity and insulin resistance (IR) co-existence with type 1 diabetes mellitus (T1DM)-related cardiovascular (CVD) complications and evaluates possible therapeutic options.

Recent Findings

Obesity and IR have increasingly been emerging in patients with T1DM. Genetic, epigenetic factors, and subcutaneous insulin administration are implicated in the pathogenesis of this coexistence. Accumulating evidence implies that the concomitant presence of obesity and IR is an independent predictor of worse CVD outcomes.

Summary

The prevalence of obesity and IR has increased in patients with T1DM. This increase can be partly attributed to general population trends but, additionally, to iatrogenic weight gain caused by insulin treatment. This association might be the missing link explaining the excess CVD burden observed in patients with T1DM despite optimal glycemic control. Data on newer agents for type 2 diabetes mellitus (T2DM) treatment are unraveling novel ways to challenge this aggravating coexistence.

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Abbreviations

AER:

Albumin excretion rate

CVD:

Cardiovascular disease

CAD:

Coronary artery disease

CACTI:

Calcification in Type 1 Diabetes Mellitus Study

DCCT:

Diabetes Control and Complications Trial

DD:

Double diabetes

EDC:

Pittsburgh Epidemiology of Diabetes Complications Study

EDIC:

Epidemiology of Diabetes Interventions and Complications study

eGDR:

Estimated glucose disposal rate

FinnDiane:

Finnish Diabetic Nephropathy Study

FTO:

Fat mass and Obesity-associated

GADA:

Glutamic acid decarboxylase antibodies

GFR:

Glomerular filtration rate

GLP-1:

Glucagon-like peptide 1 agonists

GSK-MODY:

Glucokinase Enzyme Related-Maturity-Onset Diabetes of the Young

HF:

Heart failure

HOMA:

Homeostatic model assessment

IDF:

International Diabetes Federation

LADA:

Latent autoimmune diabetes in adults

LDL-C:

Low-density lipoprotein cholesterol

MACE:

Major adverse cardiovascular events

MCR:

Melanocortin 4 receptor gene

MDI:

Multiple daily injections

miRNA:

MicroRNAs

MS:

Metabolic syndrome

NCEP:

National Cholesterol Education Program

NFκB:

Nuclear factor-κB

IR:

Insulin resistance

IMT:

Carotid intima-media thickness insulin resistance

RCT:

Randomized controlled trial

T1DM:

Type 1 diabetes mellitus

T2DM:

Type 2 diabetes mellitus

SGLT2i:

Sodium-glucose cotransporter 2 inhibitors

SNP:

Single nucleotide polymorphism

WHR:

Waist to hip ratio

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  1. First Department of Propaedeutic Internal Medicine, Medical School, National Kapodistrian University of Athens, Laiko General Hospital, 17 Agiou Thoma Street, Athens, 11527, Greece

    Georgios Karamanakos, Alexander Kokkinos & Stavros Liatis

  2. Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, Athens, Greece

    Maria Dalamaga

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Georgios Karamanakos, Maria Dalamaga declare that they have no conflict of interest. Alexander Kokkinos: Served on advisory boards, received travel grants, or research support from Eli Lilly, Sanofi, Novo Nordisk, MSD, Astra Zeneca, ELPEN Pharma, Boehringer-Ingelheim, Bausch Health, Ethicon, Galenica, and Epsilon Health. Stavros Liatis: I have received research support and/or consulting or speaker honoraria from Astra-Zeneca, Boehringer-Ingelheim, MSD, Novartis, Novo Nordisk, Sanofi, Eli Lilly, and ELPEN, during the last three years.

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Karamanakos, G., Kokkinos, A., Dalamaga, M. et al. Highlighting the Role of Obesity and Insulin Resistance in Type 1 Diabetes and Its Associated Cardiometabolic Complications. Curr Obes Rep 11, 180–202 (2022). https://doi.org/10.1007/s13679-022-00477-x

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