Insulino resistance assessment

Insulino resistance assessment

Table of Contents

{{ TableOfContents }} Inspired by a recent article by Cersosimo (2014) dealing with ways to assess insulin resistance. Completed byAntuna-Puente (2011)’s article.

Summary

  • Many assays are availlable to evaluate IR providing their own indicators:
    • research scope : clamps / suppression test;
    • clinical scope : OGTT / MTT.
  • Gold Standard is the euglycemic hyperinsulinemic clamp.
  • HOMA and QUICKI are the typical tests used in clinics;

Prior words

Insulin?

Insulin is the hormone allowing blood glucose uptake by cells to ensure their energetic needs.

Glucose cell entry Source : EthosHealth

Insulin resistance

Insulin resistance is loss of insulin cells sensitivity towards insulin. Normal physiological reaction is impaired at regulary level. More insulin is needed to get the effect.

Finally, it leads to pancreas faillure which can’t manage to produce enough insulin to obtain effects.

Importance ?

Glycemia increases and negative effects appear (neuropathies, infections, nephropathies…).

It is associated to type 2 diabetes and is part of metabolic syndrom (obesity, hyperlipemia, hypertension…).

The Tests

Insulin supression Test

Insulin Supression Test (IST) described by Shen (1970) allows a direct IR evaluation.

Principle :

  • endogene insulin suppression (i.v. somatostatin);
  • constant insulin and glucose infusion;
  • glycemia at end point is related to IR. Insulin Suppression Test Source : Shen(1970)
    Without insulin feedback, hyperglycemia rising. It’s more important in healthy subject compared to diabetics.

Evaluation after a model

An IR index is based after a complex mathematic model.

Minimal-model-based insulin sensitivity index (SI) Bergman 1979 / Pacini 1982 can be determined after easily accessible variables in clinics. HOMA and QUICKI are the most used indexes.

Index Author Notes
HOMA Matthews (1985) fasting Glycemia + insulinemia. Many evolutions including IR and insulin secretion
QUICKY Katz (2000) HOMA inverse logarithme
- Perseghin (2001) QUICKI based + non estrified fatty acids
McAuley index Mc Auley (2001) fasting triglycerides + insulin
TyG index Guerrero Romero (2010) Glucose tolerance + triglycerides + glycemia + weight
Diss index Diss (2008) HDL-chol + non esterified fatty acids + insulinemia + atherogenique index
Frequently sampled intravenous glucose tolerance test (FSIGT / IVGTT)

FSIGT ( Frequently sampled intravenous glucose tolerance test) by Bergman (1987) allows access to:

  1. SiMM (insulin sensitivity index) : link insulin level - glucose disapearance
  2. SgMM (glucose effectiveness index) : glucose effect on his own disapearance independently of insulin level.

Principle : Kinetics analyses for glycemia and insulinemia by mathematical models after iv glucose bolus.

Intravenous Glucose Tolerance Test Source : Benedini (2013)
Glycemia is increased after glucose bolus. A quick response follows a major insulin burst

Oral Tolerance Test

Glucose (OGTT)

Himsworth (1936, 1939) uses OGTT (Oral glucose tolerance Test). More “physiological” than iv infused test despite glucose input volume is not. Many variants have been developped, adapted to different populations and conditions.

Principle : Glucose ingestion then glycemia monitored 2 hours after ingestion or glycemia and insulinemia followed every 30 min depending on the parameters to determine. Glucose tolerance test Source : Wiring Diagrams
Glycemia baseline, hyperglycemic burst and back to unfavourable baseline in pathological condition.

Index Author Notes
ISI Avignon Avignon (1999) includes estimation of glucose volume distribution
ISI Belfiore Belfiore (1998) uses glucose and insulin AUC during OGTT
ISI Cederholm Cederholm (1990) uses specific points of OGTT curve
ISI Gutt Gutt (2000) derived from Cederholm
ISI Matsuda Matsuda (1999) Leader index, OGTT represents peripheral skeletal muscle
ISI Stumvoll Stumvoll (2000) adapted to varied populations, includes BMI
OGIS Mari (2001) complex equations whose parameters vary with test lenght
SI_IS OGTT Bastards (2007) log transformation with good CLAMP correlation
Liver IR Vangipurapu (2011) includes HDL-Chl, %BF, BMI

BF: Body Fat / BMI: Body Mass Index
Table inspired by ‘Antuna-Puente (2011)

Meal (MTT)

Considered closer to physiological response to a regular meal than OGTT, but hardly standardized.

Principle : Standardized caloric load is ingested, glycemia, C-peptide and insulinemia are monitored.

ISR (Insulin Secrection Rate) is determined for a latter DI (Disposition Index) evaluation.

Index Author Notes
Elrick (1964)
Caumo (2000) integral based model
Dalla Mann (2002) differential equation based model

Euglycemic clamp Source : Benedini (2013)
Glycemia increased after glucose or meal intake. Insulinemia is increased.

CLAMPS

CLAMP approach has been developped by DeFronzo. It relies on glucose homeostasy and feedback system aiming to keep a stable glycemia:

  • increased glycemia activate insulin secretion to higher cells uptake;
  • decread glycemia inhibits insulin secretion to lower cells uptake.

Stable isotopes allow access to additional parameters.

Subjecs condition / disease are supposed to have no effects on glucose non-insulin-mediated glucose uptake.

CLAMPS Principle Notes
hyperglycemic - Hyperglycemia by glucose perfusion
- Plateau
- Insulin level détermination by C-peptide deconvolution
-
cold euglycemic hyperinsulinemic - constant insuline infusion
- glucose perfusion ajustement to keep baseline glycemia
- Gold Standard
- IR determination
hot euglycemic hyperinsulinemic - Idem cold
- stable isotope labeled glucose infusion
- Hepatic resistance determination
- Access to total glucose usage mediated by insulin

Graphe: euglycemic hyperinsulinemic clamp Euglycemic clamp Source : Benedini (2013)
Stabilization time up to T120. From T120, insulin system saturation and glucose infusion adjustment to baseline glycemia.

FINALLY

The choice of test to perform depends on the context and the deepness one wants to give to IR indicator. Indicators are poorly directly comparable. Some lack of standard may require carefull analysis before interpretation.

Avatar
WPdrx
Physiologist Bioinformatician
Previous