Title : Do the STAP test --- Prevent the diabetes
Abstract:
Type 2 diabetes mellitus (T2DM), characterized by hyperglycemia (≥126 mg glucose/100 ml blood after overnight fasting) and insulin resistance, is a major global health problem. Globally, approx. 6.7 million people died from diabetes in 2021, and total health expenditure due to diabetes was $966 billion. In the USA, the direct healthcare cost of diabetes was $237 billion, 25% of the national healthcare cost.
The etiology of T2DM is poorly understood. Low-grade systemic inflammation has been implicated to play a pivotal role in the pathogenesis of T2DM. Death of intestinal microbes releases the endotoxin lipopolysaccharides (LPS) that is usually excreted with stool. However, increased gut permeability and increased intake of a high-fat diet, alcohol, and fructose, cause LPS to translocate to blood circulation. Recently, ‘metabolic endotoxemia’, defined as persistently increased levels of LPS in blood, has been shown to induce low-grade systemic inflammation leading to insulin resistance, hyperglycemia (T2DM), dyslipidemia, and fatty liver in mice.
Previously, we have shown that LPS is detoxified by intestinal alkaline phosphatase (IAP), a gut enzyme secreted by villus-associated enterocytes and excreted with stool. IAP functions as an anti-inflammatory enzyme by detoxifying LPS and other bacterial toxins through dephosphorylation. We have demonstrated that mice deficient in IAP (IAP knockout, Akp-/-) develop the metabolic syndrome (hyperglycemia, dyslipidemia, and fatty liver) that can be prevented by oral IAP supplementation.
Our subsequent case-control human study identified that the average IAP level was 35 U/g stool in diabetes patients, and it was 65 U/g stool in healthy people. Accordingly, an IAP level of ≥65 U/g stool is considered high (normal) and protective against T2DM. The obese people with normal IAP levels did not develop T2DM. We hypothesized that IAP deficiency (IAPD) might be an independent etiological factor of T2DM in humans.We conducted a 5-year prospective cohort study on a non-diabetic healthy cohort (30-60 years old), comprising 188 participants without IAPD (IAP level: ≥65 U/g stool) and 386 participants with IAPD. We measured stool IAP (STAP) and fasting plasma glucose and calculated risk ratio (RR) using the log-binomial regression model.
T2DM incidence rates were 8.0%, 11.7%, 25.6%, and 33.3% in participants with ‘persistent no IAPD’ (IAP level: always ≥65 U/g stool), ‘remittent IAPD’ (IAP level: increased from <65 to ≥65 U/g stool), ‘persistent IAPD’ (IAP level: always <65 U/g stool), and ‘incident IAPD’ (IAP level: decreased from ≥65 to <65 U/g stool), respectively. Compared to ‘persistent no IAPD’ the risk of developing T2DM with ‘incident IAPD’ was 270% higher. With ‘persistent IAPD’ the risk was 230% higher. ‘Remittent IAPD’ showed no risk.
Sensitivity analyses of persistent IAP levels revealed that compared to participants having always >115 U IAP/g stool, the rate of increase of fasting glycemia was double, and the risk of developing T2DM was 1,280% higher in participants having always <15 U IAP/g stool. A diabetes pathogenesis model is presented.We conclude that IAPD is an etiological factor of T2DM, and regular STAP tests would predict individual vulnerability to T2DM. Oral IAP supplementation might prevent T2DM.
Audience Takeaway:
•The audience will know about the breakthrough discovery that intestinal alkaline phosphatase deficiency (IAPD) causes diabetes. The audience will know about STAP test to diagnose IAPD, and thus take pre-emptive measures to prevent diabetes.
•The audience will have the knowledge on the etiology and pathogenesis of diabetes that will equip the audience to design and develop new technology for prevention of diabetes.
•Of course, other faculties will be able to use this knowledge to teach and develop new technology for prevention, treatment and cure of diabetes.
• This discovery will be able to eliminate (eradicate) 85% non-genetic diabetes.
• It is a de novo technology.
•Soon, diabetes will be a history for humanity.
