Insulin Resistance, HbA1c, Fasting Insulin, and C-Peptide: Implications for Long-Term Health in Ageing

As a clinical nutritionist, I frequently work with clients concerned about their metabolic health, especially as they age. Insulin resistance, a condition that becomes more common with advancing age, is a critical factor in the development of chronic diseases such as type 2 diabetes and cardiovascular disease. Key biomarkers including HbA1c, fasting insulin, and C-peptide provide valuable insights into metabolic health and guide interventions to promote healthy aging. At FROM WITHIN, we explore the science behind insulin resistance, HbA1c, fasting insulin, and C-peptide, their significance as we age, and their implications for long-term health.

What is Insulin Resistance?

Insulin resistance occurs when cells in the body become less responsive to insulin, a hormone that regulates blood glucose levels. This reduced sensitivity prompts the pancreas to produce more insulin, leading to hyperinsulinemia. Over time, this can impair glucose regulation, increasing the risk of type 2 diabetes and other metabolic disorders (Rojas et al., 2018). Aging exacerbates insulin resistance due to changes in body composition, such as increased visceral fat and reduced muscle mass, as well as heightened oxidative stress and inflammation (Chia et al., 2018). In Australia, where over 1.3 million people live with diabetes (Diabetes Australia, 2023), addressing insulin resistance is a public health priority.

HbA1c: A Marker of Long-Term Glucose Control

HbA1c (glycated haemoglobin) measures average blood glucose levels over the past 2–3 months by assessing the percentage of haemoglobin bound to glucose. Normal HbA1c levels are below 5.7%, with 5.7%–6.4% indicating prediabetes and ≥6.5% suggesting diabetes (American Diabetes Association, 2023). As we age, HbA1c tends to rise due to declining insulin sensitivity and pancreatic beta-cell function (Chia et al., 2018). A study by Dubowitz et al. (2019) noted that HbA1c increases slightly with age, even in non-diabetic individuals, contributing to higher risks of cardiovascular disease, kidney dysfunction, and cognitive decline (Selvin et al., 2018).

Fasting Insulin: An Early Sign of Metabolic Dysfunction

Fasting insulin measures insulin levels in the blood after an overnight fast, typically ranging from 2–25 µIU/mL, with optimal levels below 10 µIU/mL (Rojas et al., 2018). Elevated fasting insulin is an early indicator of insulin resistance, often detectable before changes in HbA1c or fasting glucose. Aging is associated with higher fasting insulin due to compensatory hyperinsulinemia (Chia et al., 2018). In Australia, where obesity affects 31% of adults (Australian Bureau of Statistics, 2022), elevated fasting insulin is a growing concern, linked to increased risks of type 2 diabetes, hypertension, and atherosclerosis (Rojas et al., 2018).

C-Peptide: A Measure of Insulin Production

C-peptide, a byproduct of insulin synthesis, is produced in equal amounts to insulin by pancreatic beta-cells and serves as a reliable marker of endogenous insulin production (Leighton et al., 2017). Unlike insulin, C-peptide is not significantly cleared by the liver, making it a more stable indicator of beta-cell function. Normal fasting C-peptide levels typically range from 0.8–3.0 ng/mL, though optimal ranges may vary slightly by laboratory standards (Jones & Hattersley, 2016).

In aging populations, C-peptide levels can reflect the degree of insulin resistance and beta-cell stress. Elevated C-peptide levels often indicate compensatory hyperinsulinemia in response to insulin resistance, while low levels may suggest beta-cell failure, as seen in advanced type 2 diabetes (Leighton et al., 2017). A study by Saisho (2016) found that C-peptide levels tend to increase with age in insulin-resistant individuals but decline in those progressing to diabetes due to beta-cell exhaustion. Measuring C-peptide alongside fasting insulin and HbA1c provides a comprehensive picture of metabolic health, particularly in older adults at risk of type 2 diabetes (Jones & Hattersley, 2016).

Implications for Long-Term Health

The interplay of insulin resistance, HbA1c, fasting insulin, and C-peptide has significant implications for long-term health, particularly as we age. Below are key consequences:

1. Type 2 Diabetes Risk

Insulin resistance drives the progression to type 2 diabetes by straining beta-cells, leading to elevated HbA1c and C-peptide levels initially, followed by potential beta-cell failure (Saisho, 2016). In Australia, the lifetime risk of type 2 diabetes is approximately one in three for men and one in four for women (Diabetes Australia, 2023). Monitoring C-peptide can help distinguish between insulin resistance and beta-cell dysfunction, guiding targeted interventions.

2. Cardiovascular Disease

Insulin resistance and hyperinsulinemia, reflected by high fasting insulin and C-peptide, contribute to cardiovascular risk through dyslipidaemia, hypertension, and endothelial dysfunction (Rojas et al., 2018). Elevated HbA1c, even in the prediabetes range, increases cardiovascular event risk by 20–30% (Selvin et al., 2018). Aging amplifies these risks due to increased arterial stiffness (Chia et al., 2018).

3. Cognitive Decline

Insulin resistance, marked by elevated HbA1c, fasting insulin, and C-peptide, is linked to cognitive impairment and Alzheimer’s disease, sometimes called “type 3 diabetes” (de la Monte, 2019). A study by Hoscheidt et al. (2017) found that higher C-peptide levels were associated with reduced cognitive performance in older adults, highlighting the brain’s sensitivity to metabolic dysfunction.

4. Other Chronic Conditions

Insulin resistance is associated with non-alcoholic fatty liver disease (NAFLD), polycystic ovary syndrome (PCOS), and certain cancers (Rojas et al., 2018). Elevated C-peptide levels have been linked to increased cancer risk, particularly colorectal and breast cancer, due to insulin’s mitogenic effects (Trabert et al., 2019). These conditions become more prevalent with age, emphasising the need for early intervention.

Strategies for Managing Insulin Resistance and Improving Metabolic Health

As a clinical nutritionist, I advocate for evidence-based lifestyle interventions to improve insulin sensitivity, lower HbA1c, normalise fasting insulin, and optimising C-peptide levels. Some practical strategies include:

1. A Low-Glycaemic, Nutrient-Dense Diet

A diet rich in whole foods, such as vegetables, fruits, whole grains, lean proteins, and healthy fats, improves insulin sensitivity. The Mediterranean diet reduces HbA1c, fasting insulin, and C-peptide levels by emphasising fibre and monounsaturated fats (Esposito et al., 2015). Limiting refined carbohydrates and sugars is essential to prevent glucose spikes.

2. Regular Physical Activity

Exercise enhances insulin sensitivity by increasing muscle glucose uptake and reducing visceral fat. Both aerobic and resistance training are effective (Karstoft et al., 2017). The Australian Physical Activity Guidelines recommend 150 minutes of moderate-intensity aerobic activity weekly, plus muscle-strengthening exercises twice weekly (Department of Health, 2021).

3. Maintain a Healthy Weight

Modest weight loss (5–10% of body weight) significantly improves insulin sensitivity, lowers HbA1c, and reduces C-peptide levels (Wing et al., 2016). In Australia, where obesity is a major issue, weight management is critical.

4. Prioritise Sleep and Stress Management

Poor sleep and chronic stress elevate cortisol, worsening insulin resistance and increasing C-peptide levels (Knutson et al., 2017). Aim for 7–9 hours of quality sleep and practice stress-reduction techniques.

5. Monitor Metabolic Markers

Regular testing of HbA1c, fasting insulin, and C-peptide can track progress and guide interventions.

Insulin resistance, elevated HbA1c, fasting insulin, and C-peptide are critical markers of metabolic health that become increasingly relevant as we age. In Australia, where metabolic disorders are on the rise, understanding these biomarkers empowers individuals to take control of their health. By adopting a low-glycaemic diet, engaging in regular exercise, maintaining a healthy weight, prioritising sleep, and monitoring metabolic markers, we can improve insulin sensitivity and reduce the risk of chronic diseases. If you want to learn more, book an appointment here today.

References

American Diabetes Association. (2023). Standards of medical care in diabetes—2023. Diabetes Care, 46(Supplement 1), S1–S291. https://doi.org/10.2337/dc23-SINT

Australian Bureau of Statistics. (2022). National Health Survey: First results, 2020–21. https://www.abs.gov.au/statistics/health/health-conditions-and-risks/national-health-survey-first-results/latest-release

Chia, C. W., Egan, J. M., & Ferrucci, L. (2018). Age-related changes in glucose metabolism, hyperglycemia, and cardiovascular risk. Circulation Research, 123(7), 886–904. https://doi.org/10.1161/CIRCRESAHA.118.312806

de la Monte, S. M. (2019). The full spectrum of Alzheimer’s disease is rooted in metabolic derangements that drive type 3 diabetes. Advances in Experimental Medicine and Biology, 1128, 45–83. https://doi.org/10.1007/978-981-13-3540-2_4

Department of Health. (2021). Physical activity and exercise guidelines for all Australians. Australian Government. https://www.health.gov.au/topics/physical-activity-and-exercise/physical-activity-and-exercise-guidelines-for-all-australians

Diabetes Australia. (2023). Diabetes in Australia. https://www.diabetesaustralia.com.au/about-diabetes/diabetes-in-australia/

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Esposito, K., Maiorino, M. I., Bellastella, G., Chiodini, P., Paternoster, D., & Giugliano, D. (2015). A journey into a Mediterranean diet and type 2 diabetes: A systematic review with meta-analyses. BMJ Open, 5(8), e008222. https://doi.org/10.1136/bmjopen-2015-008222

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