A claim you hear on longevity podcasts

Is a fasting insulin above 5 too high?

Leaning for. Of 10 studies that test it, 7 partly agree and 3 agree.

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The claim checked: A fasting insulin of 18 is not normal, and it should be 5 or less Hear it at 9:44

What do the studies say?

Leaning for

Higher fasting insulin goes with more heart disease and diabetes, but no study here tests the line said on the episode. Three of ten studies agree that risk rises with insulin across the whole range, including a pooled analysis of 22 studies. Seven are mixed. In several, insulin stopped predicting diabetes or death once other risk factors were counted. The studies that set a line put it higher: the top fifth of people, or 8 for men and 10 for women in one Brazilian study.

Computed from 10 studies that test this point, each judged by two readers, in full. 10 more studies are waiting for a full read and do not count yet.

What was said on the podcast?

“Even though 18 is considered quite normal, it's not. It should be five or less.”
Mark Hyman, The Doctor's Farmacy · Why Your Insulin Resistance Isn't Permanent (And How to Fix It) · 9:44 on YouTube
Episode check Heart risk climbs from a fasting blood sugar inside the normal range, the episode says. Four of seven studies disagree. 6 claims checked against 62 studies · 8 chapters not checked yet See the whole episode →
The point checked Leaning for

A fasting insulin above about 5, though inside the lab reference range, goes with insulin resistance or a higher risk of type 2 diabetes or cardiovascular disease

Agree 3

pooled analysis · 2013

“In this quantitative meta-analysis of prospective cohort studies, we found significant, positive, and linear associations of fasting insulin concentrations with risk of hypertension and CHD, but not stroke.”

Fasting insulin concentrations and incidence of hypertension, stroke, and coronary heart disease: a meta-analysis of prospective cohort studies. Am J Clin Nutr
Who: General-population adults without prior diagnosed CVD in 22 prospective cohort studies (USA, Europe, Japan, Korea, China)
PMID 24132974

other primary study · 2007

“The association of fasting insulin with incident outcomes was linear across the distribution with no statistical evidence from models with indicator variables or from higher-order curvilinear variables of nonlinear associations (all p -values >0.2).”

Independent associations of fasting insulin, glucose, and glycated haemoglobin with stroke and coronary heart disease in older women. PLoS Med
Who: 3,246 British women aged 60-79 from 23 towns, without diagnosed diabetes, fasting glucose below 7.0 mmol/l, and no CHD or stroke at baseline
PMID 17760500

other primary study · 2021

“We identified fasting insulin blood levels at baseline as a further strong predictor of atherogenic progression.”

The Epidemiological Boehringer Ingelheim Employee Study (Part 3): Association of Elevated Fasting Insulin Levels but Not HOMA-IR With Increased Intima Media Thickness and Arteriosclerosis in Middle-Aged Persons. Front Cardiovasc Med
Who: 1,639 middle-aged Boehringer Ingelheim employees (mean age 45, 49.4% men) without increased IMT, arteriosclerosis or other CVD at baseline
PMID 34746266

Partly agree 7

other primary study · 2009

“We conclude that in subjects with normoglycemia, basal insulin in the upper quintile confers an increased risk for the development of glucose dysmetabolism.”

Basal-state hyperinsulinemia in healthy normoglycemic adults is predictive of type 2 diabetes over a 24-year follow-up: a preliminary report. Diabetes Care
Who: 515 ethnically diverse Israeli men and women, normoglycemic at baseline in 1980 (fasting glucose 110 mg/dl or less and 2-h glucose below 140 mg/dl), mean age 70.4 at follow-up
PMID 19435961

pooled analysis · 2012 · landmark

“In a standardized meta-analysis we found that coronary heart disease risk increased with 46% for an increase of one standard deviation in HOMA-IR concentration compared to an increase of 21% for fasting glucose concentration and an increase of 4% for fasting insulin concentration.”

Insulin resistance and risk of incident cardiovascular events in adults without diabetes: meta-analysis. PLoS One
Who: Individuals without diabetes at baseline in 65 cohort or nested case-control studies; 17 studies (46,236 participants) reported fasting insulin
PMID 23300589

other primary study · 2010

“Higher serum insulin appeared to be associated with mortality, but this association did not reach statistical significance.”

Insulin resistance predicts mortality in nondiabetic individuals in the U.S. Diabetes Care
Who: 5,511 nondiabetic U.S. adults aged 20 or older from NHANES III (1988-1994) assigned to the morning fasting examination
PMID 20200308

pooled analysis · 2017

“Our meta-analysis indicated that HOMA was associated with greater risk of all-cause mortality in adults without diabetes; however, the predictive role of elevated fasting insulin itself in this process was not statistically significant.”

Fasting insulin, insulin resistance, and risk of cardiovascular or all-cause mortality in non-diabetic adults: a meta-analysis. Biosci Rep
Who: Non-diabetic adults in 7 prospective studies from the U.S.A., Europe and Korea (ages from 25 to about 76 at baseline)
PMID 28811358

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other primary study · 2018

“In multivariate adjusted models, fasting insulin was no longer associated with incident type 2 diabetes.”

Size and shape of the associations of glucose, HbA1c, insulin and HOMA-IR with incident type 2 diabetes: the Hoorn Study. Diabetologia
Who: 1,349 Dutch adults aged 50-75 (mean 60.3) without diabetes at baseline from the population-based Hoorn Study
PMID 29018885

other primary study · 2014

“All markers of IR significantly predicted an increased risk of CVD events in unadjusted models.”

Markers of tissue-specific insulin resistance predict the worsening of hyperglycemia, incident type 2 diabetes and cardiovascular disease. PLoS One
Who: Finnish men aged 45-73 from the population-based METSIM Study in Kuopio, without previously diagnosed diabetes (9,398 at baseline; 8,749 non-diabetic for follow-up)
PMID 25310839

other primary study · 2022

“The cut-offs obtained for the diagnosis of hyperinsulinemia (and raised HOMA-IR) in the present study [i.e., Men ≥ 8 mU/L (≥ 1.5), Women ≥ 10 mU/L (≥ 2.0)], are lower than those considered as the reference points by most clinical analysis laboratories.”

Proposal for standardizing normal insulin ranges in Brazilian patients and a new classification of metabolic syndrome. Front Med (Lausanne)
Who: 1,015 Brazilian adults (751 men, 264 women; mean age 46.5) attending elective check-ups at Hospital Alemão Oswaldo Cruz, São Paulo
PMID 36160146

Disagree 0· none of the studies we read

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