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Global Translational Medicine Glucosidase and metabolic profiles

The common pathophysiological sequelae of obesity and not typically found in fresher, whole foods. Although the
T2DM are approaching epidemic proportions, with no convenience of table-ready, manufactured foods may seem
clear preventative or therapeutic solutions on the horizon. advantageous to modern families, over the long term, they
1-4
As recently as 2021, the Centers for Disease Control and may be less healthful than the traditional, wholesome
1,7
Prevention estimated that over 38 million adults in the “home-cooked” meals of past generations. The influx of
United States of America had diabetes, representing more high-fructose corn syrup (HFCS) sweeteners, for example,
than 14% of the population, with over 90% of these cases has resulted in a four- to five-fold increase in fructose intake,
being a mix of diagnosed and undiagnosed T2DM – the now approaching the generally accepted safe levels of 80
most common form of diabetes worldwide, affecting – 100 mg/day. This intake comprises up to 20% or more
over 800 million individuals. Dietary, medication, and of daily caloric intake for many individuals consuming
4,5
lifestyle changes remain the hallmark of conventional processed foods and beverages. The excess consumption
8
therapeutic approaches to treat the diabetes element of HFCS-containing foods and beverages may further
of obesity, aimed at improving glycemic markers. disrupt optimal metabolic pathways in glycolysis and
8
Unfortunately, present approaches to reducing the burden substrate oxidation. Healthful dietary changes are often
of obesity and T2DM, although well-intentioned, are often challenging to implement in a population accustomed
less than fully successful. The common clinical sequelae to the convenience and prevalence of industrialized food
of obesity and T2DM, arising from long-standing dietary choices, where the inclusion of lipids and sweeteners,
and lifestyle factors, may have been largely asymptomatic along with the ease of meal preparation, adds to their
3-8
before diagnosis, making them not immediately reversible. palatability, popularity, and convenience. In addition,
Long-held dietary and lifestyle habits can be difficult the modernization of the food supply’s macronutrient
to change, and even when modifications are made, the and micronutrient composition may not be adequate
pathophysiologic progression of typical sequelae may be to address chronic insulin resistance and associated
firmly established, with incomplete reversibility occurring systemic inflammation common in obese and T2DM
7
over the weeks or months following the initiation of states. Moreover, once diagnosed, diabetes treatment is
therapeutic measures. While glycemic improvement typically long-term and may continue for the remainder of
may begin shortly after the implementation of dietary or a patient’s life. 6-8
luminal therapeutic interventions, restoration of plasma The magnitude and duration of the insulin response to
lipid profiles typically takes longer and resolves more a meal are generally proportional to the type, quality, and
gradually, requiring long-term interventions to normalize. quantity of the carbohydrates consumed. The compound
In addition, once systemic inflammation and advanced 1,5 dideoxy-1,5-[(2-hydroxyethyl) imino]-D glucitol
states of atheroma and vascular plaque have developed, full (generic name: Miglitol [MIG]; marketed as Glyset ) is
®
recovery, including atheromatous reversal, may be difficult an established competitive inhibitor of luminal starch
to achieve. 5,6 digestion, acting within the brush border α-glucosidase
Chronic elevations in plasma lipid profiles are receptor domains of the small intestine. 9-13 Once the
common observations in obesity and T2DM, contributing compound competitively binds to the glucosidase receptor
to the progression of cardiovascular disorders often domains, it effectively delays the rate-limiting process of
1-4
associated with these conditions. In addition, chronic starch digestion into absorbable monosaccharide units,
hyperinsulinemia contributes to systemic inflammation thereby reducing subsequent luminal glucose uptake from
9
in the central nervous system and other tissues, adding the gastrointestinal tract. Unlike some other α-glucosidase
to the pathophysiologic burden of the disorder. inhibitors, MIG is fully or nearly fully absorbed in the
4-6
Thus, implementing therapeutic measures to reduce small intestine but escapes hepatic P-450 metabolism and
inflammation and decrease elevated triglycerides, total conjugation, being cleared by the kidneys without further
metabolism within a few hours of ingestion. As the typical
9
cholesterol, and low-density lipoprotein cholesterol (LDL- intestinal starch digestive process occurs rapidly, the
C) is considered essential and desirable for long-term generation of monosaccharide units is the rate-limiting
treatment goals, often requiring prolonged intervention to step in glucose uptake. Post-ingestive glycemic excursions
achieve satisfactory progress. 2 are proportional to the rate of dietary post-ingestive
The industrialization of the food supply chain has α-glucosidase activity. Dietary sources of fructose may
introduced dietary changes in industrialized populations, result from the luminal digestion of sucrose into its
including a greater abundance of commercially processed constituent glucose and fructose monosaccharide units
foods. While many processed foods retain nutritional or from free fructose contained in foods and beverages.
qualities, they often contain excess salts and preservatives However, fructose uptake occurs more slowly than glucose,

Volume 4 Issue 2 (2025) 59 doi: 10.36922/gtm.6501