The term prediabetes refers to blood sugar levels that are higher than average but not high enough to be identified as diabetes. This article elucidates prediabetes, and its associated health conditions along with a case study presentation.

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Prediabetes

Prediabetes is defined as fasting plasma glucose (FPG) of 100–125 mg/dL, 2-h postprandial blood glucose (2 h PG) of 140–199 mg/dL or HbA1c of 5.7%–6.4% (ADA guidelines).

Even though the haemoglobin A1c and blood sugar levels in prediabetic patients appear normal, it takes a significant quantity of insulin to raise the blood sugar levels to normal. Insulin resistance is the reason for this very high insulin requirement. This is the hidden glacier, the cardinal feature of prediabetes.

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Diagnosis

Patients with type 2 DM typically do not receive the diagnosis until several years after disease onset. Although recent data are lacking, older studies estimate patients with type 2 DM live with the disease approximately 4-7 years before its diagnosis. Unlike the sudden and symptomatic onset of type 1 DM, type 2 DM has a gradual and asymptomatic onset. This asymptomatic nature of early type 2 DM creates a diagnostic challenge for clinicians, one that underscores the importance of obtaining a thorough patient history to identify at-risk patients.

When the body produces significant amounts of insulin, the blood sugar level may no longer stay low, leading to a late diagnosis of diabetes. As you can see, the early detection of hyperinsulinemia can have a significant impact on the development of atherosclerosis and diabetes in the future.

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Associated health risks 

The body is adversely affected by abnormally high insulin levels even while the sugar and haemoglobin A1c levels appear normal: causes vascular disease, low HDL, high triglycerides, small dense LDL particles, atherosclerosis, risk of heart attacks and strokes, abdominal adiposity, fatty liver, visceral fat (weight around the waist).

Prediabetics have been found to have a 20% more increased risk of developing CVD than euglycemic individuals. This increased risk for CVD in prediabetes is multifactorial, with etiologies including insulin resistance, dyslipidemia, hypertension, systemic inflammation, and oxidative stress. Higher triglyceride/high-density lipoprotein (TG/HDL) levels have been linked to an increased risk of cardiovascular disease (CVD) in people with dyslipidemia via impairing vessel wall integrity and inducing insulin resistance.

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Insulin levels in prediabetics

Normally, insulin peak is seen between 30 to 60 minutes, but in prediabetes or T2DM, there is a delayed peak due to insulin resistance. A key research paper published in 1975 by Dr Joseph R Kraft comprised 3650 patients who were randomly referred for glucose tolerance testing. Dr Kraft described five different insulin patterns in response to a 100 g glucose load administered over 3–5 hours with insulin levels assessed at baseline, 30, 60, 120, and at minimum, 180 min.

It entails giving a glucose solution and checking insulin levels at predetermined intervals thereafter. In the context of prediabetes, the Kraft test can help identify individuals who may be at risk for developing type 2 diabetes due to insulin resistance. Elevated insulin levels in response to glucose may indicate insulin resistance, a hallmark of prediabetes. This test can provide valuable information for early intervention and lifestyle modifications to prevent the progression of diabetes.

Pattern I: Normal

• Normal fasting insulin 0-10 units
• Peak insulin at ½-1 hour
• 2nd hour insulin <50
• 3rd hour insulin < 2nd hour
• 2nd hour + 3rd hour totals < 60
• Subsequent values at fasting range (0-10)

Pattern II: Delayed insulin peak

• Normal fasting insulin 0-10 units
• Peak insulin at ½-1 hour
• 2nd hour + 3rd hour totals > 60 and <100 = Borderline insulin resistance 2nd hour + 3rd hour totals > 100 = definite insulin resistance

Pattern III-A: Insulin resistance

• Normal fasting insulin 0-10 units
• Peak insulin at 2nd hour
• Regarded as a diagnostic tool for insulin resistance glucose tolerance can be normal or compromised

Pattern III-B: Insulin resistance

• Normal fasting insulin 0-10 units
• Peak insulin at 3rd hour
• Considered a diagnostic indicator of insulin resistance Typically, glucose tolerance is at diabetes levels

Pattern IV: Insulin resistance

• Fasting insulin >10
• Diagnostic for insulin resistance
• Glucose tolerance is usually at diabetic levels

Pattern V: Insulinopenic

• A high glucose level is regarded as a Type I Diabetes pattern
• All tested values for insulin <30
• Insulin deficiency most likely results from worn-out or damaged islet cells
• Glucose tolerance is usually at diabetic levels
• This may signal the need for exogenous insulin
• When seen with normal glucose values, may be indicative of an extremely low carbohydrate diet

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The Kraft prediabetes profile

Based on the research of Dr. Joseph Kraft, this test finds patterns that show how insulin resistance and islet cell exhaustion progress from a normal insulin response:

1. To simplify this test, we can measure a post-prandial insulin level, that is a 2-hour insulin test. If that comes normal (<60 micro units/ml) we can proceed to a 3-hour insulin test.
2. But if the 2-hour insulin test is above 60, then we don't need to proceed for the 3-hour insulin test and diagnoses of prediabetes or insulin resistance can be made along with other clinical factors. (PCOD, Acanthosis nigricans, Obesity, Euglycemic CAD)
3. The results of this test confirm the presence of insulin resistance, hyperinsulinemia, and a high cardiovascular risk.
4. It is also known as a cardiometabolic syndrome.
5. This is a very major cardiac risk factor.
6. Insulin resistance can be effectively reversed once it has been identified.

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Case study

A 17-year-old female student with a history of PCOD & anxiety came to our clinic, we suggested her post-prandial insulin test (After 2 hours), which came 74.39 micro units /ml & was diagnosed with Prediabetes (insulin resistance).

A 40-year-old male, a physiotherapist by profession, with a history of anxiety and a family history of T2DM came to our clinic. We suggested FBS, HbA1C & Random Insulin Test, which came 135 mg/dl, 7.5% and 65 respectively, and was diagnosed with T2DM. Both of them were treated individually.

Disclaimer- The views and opinions expressed in this article are those of the author and do not necessarily reflect the official policy or position of M3 India.

About the author of this article: Dr Sheikh Shafeeq Palesmir is a Consultant in Diabetology & Metabolic Medicine, based in Kashmir.