WORLD DIABETES DAY-JUST AROUND THE CORNER

World Diabetes Day is a few days away-November 14. The theme for this year’s event is “Family and Diabetes”. Families are urged to learn more about the warning signs of diabetes and find out their risk to type 2 diabetes (T2DM).Research conducted in 2018 discovered that parents would struggle to spot this serious life-long condition in their own children. Despite the majority of people surveyed having a family member with diabetes, an alarming four-in-five parents would have trouble recognizing the warning signs. One-in-three would not spot them at all.

In type 2 diabetes, the warning signs are milder even though it is the most prevalent form of diabetes (about 90%). One in two people currently living with diabetes are undiagnosed with the vast majority of these having type 2 diabetes. The complications of diabetes include blindness, amputation, kidney failure, heart attack and stroke. This then brings me to a condition that has engaged the attention health care providers’ lately-metabolic syndrome. Metabolic syndrome is a cluster of related conditions that increasesan individual’s risk for developing cardiovascular disease and Type 2diabetesmellitus (T2DM). The components ofmetabolic syndrome (MS)include abdominal obesity, dyslipidemia, elevated blood pressure,insulin resistance, glucose intolerance, β-cell loss, low-grade chronicinflammation and a prothombotic state.Strat et al. Mechanisms by which cocoa flavanols improve metabolic syndrome andrelated disorders. Journal of Nutritional Biochemistry.35 (2016) 1-21.

Dear reader, you would have noticed by now, my strenuous efforts to kindly let you appreciate the role of diet (especially increasing consumption of functional foods), lifestyle modifications in the prevention and control of some disease conditions.

The paper referred to therefore noted that increasing attention has been directed toward findingnovel strategies to prevent, slow the onset and/or progression of andpotentially reverse metabolic syndrome.Dietary flavanols offer an interesting potential complementarystrategy that may improve this complex, multifaceted syndrome. First,flavanols may help reduce glucose excursion by slowing digestion andenhancing the incretin response. Second, flavanols may help reducesystemic endotoxin exposure via improvement in gut barrier function.Flavanols are found in a variety of dietary plantssuch as tea, apples, grapes, cocoa, berries, plums, apricots and nuts.

Cocoa is generally regarded as themost concentrated dietary source of flavanols with the strongestantioxidant potential.Although cocoa contains over 350 potentially bioactive compounds, many of the health benefits are attributed to its high content (on a weight basis) of flavanols. The literature on the cardiovascular effects of cocoa is large. The link betweencocoa and improvements to metabolic syndrome and, specifically,glucose homeostasis and diabetes is equally gaining currency. Flavanols improve glucose homeostasis is by slowing carbohydrate digestionand absorption in the gut. A component of metabolic syndrome is derangement of glucosehomeostasis, resulting in hyperglycemia and glucose intolerance.Glucose levels are primarily controlled by the hormones insulin andglucagon. These two hormones are under tight regulation in order tomaintain blood glucose levels between 4.0 and 7.0 mM in normalindividuals (glucose homeostasis). Failure to maintain glucosehomeostasis can lead to a wide variety of conditions such asadiposity, dyslipidemia, vascular damage, vision loss, kidney disease,neuropathy, atherosclerosis and myocardial infarction.

When the insulin signaling pathway is impaired (e.g. dueto chronic inflammation), a cyclical effect occurs where bloodglucose levels become elevated and β-cells are constantly stimulated. This causes β-cells to deteriorate and lose their ability to produceinsulin, leading to prediabetes, T2DM and then frank diabetes with β-cell failure. Inadequate insulin secretion can then lead to hyperglycaemiaand ketoacidosis.

Cocoa can slow the rate and extent of macronutrient digestion bybinding to and antagonizing digestive enzymes such asα-amylase- the enzyme that breaks downstarch into glucose oligomers. As a result flavanols may reducedigestion of starches, thereby lowering glucose absorption viainhibiting this enzyme in the diabetic population. It is worthy of note that α-amylase expression is higher in individuals with T2DM than healthyindividuals.

Flavanolsmay also inhibit α-glucosidase, an enzyme that cleaves small oligosaccharides and result in monomeric sugarsthat are ready for absorption. Alpha-glucosidase is another key enzyme involved incarbohydrate digestion. When these enzymes are inhibited, thebreakdown of carbohydrates is slowed, resulting in an attenuatedelevation of blood glucose after a meal. Cocoa also inhibitspancreatic amylase, pancreatic lipase and phospholipase A2.Reducing rapid increases in blood glucose after ameal is important for patients with metabolic disorders, since it helpsthem maintain glucose homeostasis.

Cocoa polyphenols inhibit glucose transporters. Inhibiting glucose transporters in theintestine could attenuate glucose excursion after a meal. Intestinaltransporters that may be inhibited include glucose transporter 2(GLUT2) and sodium/glucose cotransporter 1 (SGLT1). I do know that some persons reading will appreciate that these actions of flavanol-rich cocoa are akin to some of the molecules in use for certain conditions. The intention is not for one to discontinue medications but appreciate the tremendous complementary role of flavanol-rich in such situations.

Another area is cocoa ability to enhance incretin response.Incretins, glucagon-like peptide (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are secreted from entero-endocrine cells after ameal. One of the roles of these hormones is to stimulate insulinsecretion for glucose disposal. Incretin hormones have othereffects on the pancreas, including increasing somatostatin secretion, decreasing glucagon secretion and stimulating β-cell growth andneogenesis.

Otherincretin functions include suppressing appetite, delaying gastricemptying and increasing glycogen synthesis. A key advantage in persons with pre-diabetes, or diabetes. The incretinresponse is impaired in T2DM. Cocoa enhances the incretin response byeither stimulating incretin release or extending the half-life of incretinhormones. Another clear complementary role of cocoa in persons with T2DM and on medications based on their incretin response.

Deterioration of functional β-cell mass is observed during T2DMand metabolic syndrome disease progression. Functional β-cell mass isdefined as the β-cell insulin secretion rate. The total β-cell mass is afactor of cellular proliferation and cellular death. Decreasedfunctional β-cell mass critically impinges on the ability to maintain normoglycemia. Polyphenol-rich cocoa protectsβ-cells against death-inducing damagingfactors, enhance glucose stimulated insulin secretion and induce β-cellreplication.

T2DM and other metabolic diseases are associated with chronic,low-grade inflammation and excess reactive oxygen species,which candamage β-cells, thereby further exacerbating metabolic instability.Individualswithmetabolic disorders can also presentwith a decrease inantioxidant potential (i.e., glutathione levels), so a dietary antioxidant is beneficial for the health of these patients.

Cocoa exerts protective effects on β-cells by inhibiting lipidaccumulation in the cells. While peripheral insulin resistance iscommon during obesity and aging inpeople, its progressionto T2DM is largely due to insulin secretory dysfunction and significantapoptosis of functional β-cells. Current evidence indicates that chronic hyperlipidemia (lipotoxicity) causes β-cell apoptosis andimpairs its function, thereby contributing to the pathogenesis of T2DM. Cocoa induces β-cell proliferation and beneficial to persons with T2DM ormetabolic syndrome.

Glucose intolerance and insulin resistance are characteristic of metabolic syndrome. Dietarycomponents aiding in either insulin secretion or insulin action wouldprove beneficial for patients with metabolic syndrome.

Cardiovascular health is an important facet of metabolic syndrome. Oxidative stress is present in obesity and metabolic syndrome.Reactive oxygen species can accumulate in metabolically active tissuesand cause lipid peroxidation, damage β-cells, modulate the gutmicrobiota and hinder cardiovascular function, insulin signaling andmitochondrial function. Flavanol-rich cocoa reduces the bad cholesterol (LDL) and increases good cholesterol (HDL). I believe, dear reader, you fully see the reason for defining metabolic syndrome as a complex, multifaceted disease condition and the significant benefit  of polyphenol-rich cocoa in this disease condition.

DR. EDWARD O. AMPORFUL

CHIEF PHARMACIST

COCOA CLINIC