Early Metabolic Imbalance (EMI): The Elephant in the Room

Something obvious -- and important -- is being overlooked in healthcare.

At a routine primary care visit, providers typically order blood tests such as a complete blood count (CBC), comprehensive metabolic panel (CMP), lipid panel, and hemoglobin A1c. Together, these tests screen for blood cell health, liver and kidney function, glucose tolerance, and lipid transport.

But they don’t screen for early insulin resistance or its conjoined twin, hyperinsulinemia (high levels of insulin in the blood).

Insulin resistance is simply the loss of insulin sensitivity. Muscle, liver, and adipose tissue cells become less responsive to insulin’s signal to clear glucose and lipids from the bloodstream. Insulin is knocking on the door, but the cells hesitate to open it.

In the early stage, the body compensates. Higher levels of circulating insulin are required to keep glucose and lipids in the normal range. Insulin is no longer knocking. It’s pounding.

Because this stage involves more than insulin resistance alone, we call it Early Metabolic Imbalance (EMI). It is the Yellow Zone of the Metabolism Spectrum. It is the elephant in the room.

The pancreatic beta cells are the body’s insulin factories. In healthy metabolism, normal insulin sensitivity is matched by normal insulin secretion.

In EMI, however, the drop in insulin sensitivity forces the pancreas to ramp up insulin secretion to maintain normal blood values.

This compensation works, but only temporarily.

Beta cells can sustain high insulin output for months or even years, but not indefinitely. Over time, they wear down, malfunction, and some die. This slow decline is how prediabetes and type 2 diabetes develop -- quietly and progressively.

Once the remaining beta cells can no longer meet demand, late insulin resistance sets in. Glucose tolerance and lipid transport deteriorate, leading to elevated fasting glucose, hemoglobin A1c, and triglycerides, along with reduced HDL. Clinically, this stage is labeled prediabetes or metabolic syndrome. On the Metabolism Spectrum, it’s the Orange Zone.

The figure below illustrates how insulin sensitivity, glucose tolerance, and lipid transport change across the Metabolism Spectrum. The earliest abnormality on the path toward diabetes and cardiovascular disease is the loss of insulin sensitivity: first seen in EMI, the Yellow Zone.

This post focused on EMI, the elephant in the room. In the next post, I’ll outline seven reasons why EMI is routinely missed in conventional healthcare screening.

References

Cistola DP, Cistola AS, Dwivedi AK (2026) Early Metabolic Imbalance in Lean Young Adults is a Risk Factor for Midlife Obesity. Circulation, in press. American Heart Association Epi | Lifestyle Scientific Sessions, March 2026, Boston, Massachusetts, USA.

Cistola DP, Cistola AS, Dwivedi AK (2026) Early Metabolic Imbalance in Lean Young Adults is a Risk Factor for Midlife Obesity. Circulation, in press. Lippincott Williams & Wilkins.

Cistola DP, Dwivedi AK. (2023) EMI Not Just BMI: Unveiling Hidden Diabetes Risk Among Apparently Healthy U.S. Young Adults. Metabolism 142(S), 155469, Elsevier; https://doi.org/10.1016/j.metabol.2023.155469.

Cistola DP, Dwivedi AK (2023) Early Metabolic Imbalance in Young Adults is a Hidden Risk Factor for Midlife Cardiovascular Disease: CARDIA 35-year Follow Up (2023) Circulation 147, AP336, Lippincott, Williams & Wilkins; https://www.ahajournals.org/doi/10.1161/circ.147.suppl_1.P336.

Cistola DP, Mendiola LI, Dwivedi AK. Hypoxia Response Markers are Associated with Early Metabolic Imbalance: The U.S. National Health and Nutrition Examination Survey. Circulation 151(Suppl_1), P1153. https://www.ahajournals.org/doi/10.1161/cir.151.suppl_1.P1153.

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Matsuda M, DeFronzo RA (1999) Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 22(9), 1462-1470. https://doi.org/10.2337/diacare.22.9.1462. 

Sacks DB et al. (2023) Guidelines and Recommendations for Laboratory Analysis in the Diagnosis and Management of Diabetes Mellitus. Diabetes Care 46(10), e151-e199. https://doi.org/10.2337/dci23-0036.

Cistola DP, Dwivedi AK (2025) Plasma and Serum Water T2 are Strong Predictors of Cardiometabolic Health: Implications for Point-Of-Care Screening. Circulation 151(Suppl_1), P3004. Lippincott Williams & Wilkins. https://www.ahajournals.org/doi/10.1161/cir.151.suppl_1.P3004.

Cistola DP, Patel V, Deodhar S, Mishra I, Robinson MD, Dwivedi AK. Whole Blood T2P Links Hemoglobin Status to Cardiometabolic Health. (2023) American Journal for Preventative Cardiology 15S, 100576, Elsevier. https://doi.org/10.1016/j.ajpc.2023.100576

Mishra I, Jones C, Patel V, Deodhar S, Cistola DP. (2018) Early detection of metabolic dysregulation using water T(2) analysis of biobanked samples. Diabetes Metab Syndr Obes. 2018;11:807-818. doi: 10.2147/DMSO.S180655. eCollection 2018. PubMed PMID: 30538517; PubMed Central PMCID: PMC6260129.

Robinson MD, Mishra I, Deodhar S, Patel V, Gordon KV, Vintimilla R, Brown K, Johnson L, O’Bryant S, Cistola DP. (2017) Water T(2) as an early, global and practical biomarker for metabolic syndrome: an observational cross-sectional study. Journal of Translational Medicine 2017 Dec 19;15(1):258. doi: 10.1186/s12967-017-1359-5. PubMed PMID: 29258604; PubMed Central PMCID: PMC5738216.

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