A claim you hear on longevity podcasts
Strong consensus for. Of 5 studies that test it, 3 agree and 2 partly agree.
The claim checked: Insulin goes up first, and blood sugar is the last thing to rise Hear it at 1:38
Three studies agree and two are mixed. In 515 Israeli adults with normal blood sugar, fasting insulin was the strongest sign of who got type 2 diabetes over 24 years. In British civil servants, insulin output rose up to 7 years before diagnosis. In the two mixed studies, from Britain and Denmark, people who later got diabetes already had higher blood sugar and higher insulin when first tested, as early as 13 years before diagnosis. So those studies cannot say which rose first.
Computed from 5 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.
“Because your blood sugar is the last thing to go up when you're in a metabolic dysfunction. It's the last thing to go up. The first thing up is your your insulin.”
other primary study · 2009
“Basal insulin was the strongest predictor for progression to type 2 diabetes over 24 years.”
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
other primary study · 2017
“A compensatory increase in insulin secretion alongside decreasing insulin sensitivity was observed among white individuals up to 7 years before diagnosis.”
Trajectories of glycaemia, insulin sensitivity and insulin secretion in South Asian and white individuals before diagnosis of type 2 diabetes: a longitudinal analysis from the Whitehall II cohort study. Diabetologia
Who: 987 Whitehall II British civil servants (120 South Asian, 867 white) who developed type 2 diabetes between 1991 and 2013; median age at diagnosis 63
PMID 28409212
trial or observed group · 2018
“The follow-up data in the adult cohort demonstrate that primary insulin hypersecretion is a risk factor for progression of dysglycemia.”
Identification, pathophysiology, and clinical implications of primary insulin hypersecretion in nondiabetic adults and adolescents. JCI Insight
Who: 1,168 clinically healthy European adults aged 30-60 with normal glucose tolerance (RISC study), plus a validation cohort of 182 obese nondiabetic White American and African American adolescents aged 10-20
PMID 30568042
other primary study · 2009 · landmark
“Among individuals who developed diabetes, the levels of fasting and postload glucose and insulin secretion were higher and insulin sensitivity was lower than those among the controls already 13 years before the diagnosis.”
Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall II study. Lancet
Who: 6,538 British civil servants (70.7% male, 91.3% Caucasian) free of diabetes at baseline in the Whitehall II cohort
PMID 19515410
other primary study · 2009
“At baseline, plasma glucose and insulin levels were higher, and ISI, HOMA-IS, EPIR, and DI were lower in individuals who progressed to i-IFG, i-IGT, or IFG/IGT than in those who maintained NGT status.”
Natural history of insulin sensitivity and insulin secretion in the progression from normal glucose tolerance to impaired fasting glycemia and impaired glucose tolerance: the Inter99 study. Diabetes Care
Who: 3,145 Danish adults with normal glucose tolerance at baseline from the population-based Inter99 study
PMID 19056613
Three studies agree and two are mixed. In three, groups with normal blood sugar on a glucose test still had high insulin or insulin resistance, in Finland, Qatar and Taiwan. In 6247 young American adults, 42.1% had insulin resistance, but that group included people with prediabetes, not only normal blood sugar.
Computed from 5 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.
other primary study · 2019
“The results also carry practical significance: we found that IR-associated metabolic aberrations exist already in participants with normal glucose tolerance (with implications for CVD risk) and are similar in extent to those observed in type 2 diabetes.”
Insulin resistance and systemic metabolic changes in oral glucose tolerance test in 5340 individuals: an interventional study. BMC Med
Who: Finnish adults free of diagnosed diabetes: 4745 aged 46 (NFBC66, 44% men) and 595 aged 69 (Oulu1945) undergoing a 4-time-point 75 g OGTT; 2847 NFBC66 participants had normal fasting and 2-h glucose
PMID 31779625
other primary study · 2021
“By study design all participants had normal glucose tolerance as assessed by OGTT ( figure 3 ); however, an exaggerated insulin (p<0.01) and C peptide (p<0.01) response was noted in the least and the intermediate sensitivity groups as compared with the most sensitive group ( figure 3A, B ).”
Insulin sensitivity variations in apparently healthy Arab male subjects: correlation with insulin and C peptide. BMJ Open Diabetes Res Care
Who: Apparently healthy Arab men in Qatar aged 18-45, BMI <=28, no chronic medications, normoglycemic by fasting glucose <5.6 mmol/L, 2-h OGTT glucose <7.8 mmol/L and HbA1c <5.6%; 77% had a family history of T2D
PMID 34785564
other primary study · 2014
“After adjusting for age and BMI, Group 3 also had higher FPI, OGTT120g, OGTT120i, and HOMA-IR values than the other 2 groups.”
Identification of insulin resistance in subjects with normal glucose tolerance. Ann Acad Med Singap
Who: 292 Chinese adults in Taiwan with normal glucose tolerance (ADA 2003 criteria; frank diabetes, IFG and IGT excluded), mean age about 45, self- or health-professional-referred for diabetes screening
PMID 24652432
other primary study · 2022
“Among 6247 young adults 18 to 44 years old, 42.1% had IR.”
Insulin Resistance and Cardiometabolic Risk Profile Among Nondiabetic American Young Adults: Insights From NHANES. J Clin Endocrinol Metab
Who: US adults aged 18-44 without diabetes (no antidiabetic medication, fasting glucose <126 mg/dL, HbA1c <6.5%) or preexisting cardiovascular or kidney disease, NHANES 2007-2018
PMID 34473288
other primary study · 2010
“In this study, despite little change in the distribution of FPG levels, HbA1c and FI levels increased between the two survey periods.”
Recent population changes in HbA(1c) and fasting insulin concentrations among US adults with preserved glucose homeostasis. Diabetologia
Who: Non-diabetic US adults aged >=20 (no physician-diagnosed diabetes, FPG <7.0 mmol/l), NHANES 1988-1994 vs 1999-2006
PMID 20517591
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