Diabetes is a disease caused as a result of chronic metabolic dysfunction of glucose, a principal energy source of the body cells. Glucose is obtained from dietary carbohydrates and synthesized in the body from a substrate of fatty acids and amino acids. The major and most important hormone that is required for glucose metabolism is insulin, which is produced and secreted from pancreatic islets β cells. Due to the lack of insulin secretion and the increase of insulin resistance the blood glucose rises and causes diabetes.

There are two major types of diabetes:

Type 1 Diabetes: This occurs when a significant amount of insulin secretion is reduced and 60-70% deaths of pancreatic beta-cells are observed. Immediate medical attention and insulin therapy is necessary. Type 1 occurs in a low percentage of the diabetic population.

Type 2 Diabetes: This occurs when a gradual reduction of insulin secretion is observed due to malfunction of pancreatic beta cells and/or the development of insulin resistance due to inefficiency in glucose metabolism. Type 2 is the most prevalent form of Diabetes.

The glucose homeostasis is very important for good health, where fasting glucose should be in the range of 70 mg/dL to 120 mg/dL. Outside of this range is referred to as diabetes. Below the lower limit is called hypoglycemia (low sugar) and above the upper limit is called hyperglycemia (high sugar). People with Diabetes can have significant variations of glucose levels in a 24 hour time period. Since insulin secretion is reduced, the high level of glucose remains in the blood all the time AND as time passes the high sugar in blood causes a series of health complications/diseases.

Insulin Functions:

1. Insulin facilitates entry of glucose into muscle, adipose and several other tissues
2. Insulin stimulates the liver to store glucose in the form of glycogen.
3. Insulin promotes a synthesis of fatty acids in the liver.
4. Insulin inhibits breakdown of fat in adipose tissue.
5. Insulin activates sodium-potassium ATPases in many cells, causing a flux of potassium into cells.

The regulation of insulin secretion from the ß-cell of the pancreatic islets is complex, including nervous mechanism, circulating nutrients, endocrines, and gastrointestinal hormones;

• New research suggests that normal glucose regulation depends on a partnership between the insulin-producing ß-cells of the pancreas and neuronal circuits in the hypothalamus areas that are ultimately involved in maintaining normal glucose.
• Circulating nutrients depends on the food intake type, quantity and frequency as well as synthesis of glucose within the body, especially in the liver and kidney from the fatty acids, lactate and amino acids. The re-absorption process of kidneys also plays a role in maintaining circulatory nutrients.
• Endocrines hormones from the pancreas (insulin, Glucagon, Somastatin etc), from thyroid (T3, T4, TSH) play a major part in the glucose metabolism process, metabolism rates, glucose utilization process, energy production process, and energy transportation process.
• Gastrointestinal peptides like GLP 1 and GIP also a play role in the regulation of insulin secretion as well as glucose absorption process.

In general, all of the above mentioned activities and functions play a role in maintaining glucose homeostasis. Due to inefficient activities and dysfunctions, most of the time it fails to maintains glucose homeostasis in diabetes. The diabetes reflect significant changes in various glucose metabolism processes and breaks down the body's normal glucose balancing process to maintain glucose homeostasis. In diabetes, it is important to know some facts that cause reducing insulin secretion:

1. The insulin secretion is diminished due to pancreatic ß-cell dysfunctions that lead towards apoptosis.
2. The pancreatic ß-cell dysfunctions due to the inadequate glucose metabolic process, lack of enough energy production, and increased level of ROS in mitochondria.
3. Uncontrolled glucose entry in the pancreatic cells through GLUT-2 itself can impair the insulin secretion process.
4. If the pancreatic cells fail to produce enough energy to block the KATP channel which is required for voltage guided Ca²⁺ opening to push insulin secretion.

All of the above resulted due to uncontrolled glucose metabolism process with the occurrence of pancreatic ß-cells, making the cell dysfunctional. In order to maintain the respective cell's vitality, the daily intake of micronutrients, vitamins, and antioxidants are essential. Taking these as supplements benefits the pancreatic cell's functionality and slowly improves all the pancreatic endocrine hormone secretions processes, including insulin.

Cell dysfunction and ROS: Pancreatic ß-cells as well as other body cells are affected due to reactive oxygen species (ROS) produced during all metabolic reactions and processes, especially the energy transportation system.

Beta cell demise and dysfunction involve Cytokines, Oxidative stress, Endoplasmic Reticulum stress, and inflammation.

• Specific pro-inflammation cytokines induce an inflammatory response
• Pro-inflammatory cytokines cause beta cell death via the induction of mitochondrial stress and other responses.
• Obesity is a state of low-grade inflammation. The pathogenesis of beta cell function may, to a certain extent, mimic steotosis; intra-tissue fat deposits induce inflammation thereby triggering cellular demise and dysfunction
• Cytokines secreted by immune cells that have infiltrated the pancreas are reported to be crucial mediators of beta cell destruction.
• Chronic exposure of high blood glucose, leading to oxidative stress and inflammation may induce changes in the regulation of gene expression that converge on impaired insulin secretion and increased apoptosis.
• Oxidative stress leads to damage in organelles, particularly mitochondria and cellular proteins, lipids and nucleic acid.
• Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS) form both cytokine-mediated pro-inflammatory beta cell aggression in type-1 diabetes and glucolipotoxicity-mediated beta cell dysfunction in type-2 diabetes.
• Increased ROS production from mitochondria and RNS from excess nitric oxide (NO) production in beta cells lead to the inhibition of electron transport chain resulting in reduced energy production, DNA damage, and formation of Advanced Glycation End Products (AGEs)

All these conditions are due to imbalanced or reduced availability of nutrients to beta cells, small repeated increase in ROS production, lower ATP (energy) synthesis, and inadequate antioxidant balance may pre-dispose to beta cell dysfunction.

Glucose metabolism pathways include

Energy Production Pathway (Pyruvate Production) And Pentose Phosphate Pathways

1. glycolysis (break down of glucose into pyruvate by cells for the production of energy as ATP),
2. gluconeogenesis (synthesis of glucose from non-carbohydrate precursors, lactic acid, glycerol, amino acid, mainly in the liver ),
3. Glycogenesis (formation of glycogen, glucose stored in the liver and muscle cells. Only liver glycogen converted into glucose can enter in the circulatory system)
4. Glycogenolysis (breakdown of glycogen-polysaccharide into glucose molecules-monosaccharide)
5. Glucose for energy production: in cytoplasm, in mitochondria, aerobic condition, and anaerobic condition.

Glucose for energy production pathways:

The Pentose Phosphate Pathway (PPP) (also called the "Phosphogluconate Pathway" and the "hexose monophophate shunt"): is a metabolic pathway parallel to glycolysis, occurs only in cytoplasm. It generates NADPH and Pentoses (5 carbon sugar) as well as ribose 5-phosphate (Precursor for the synthesis is nucleotide).

Note: PPP is a complex enzymatic pathway that cell carries out the direct aerobic oxidation of phosphorylated glucose into CO₂ and H₂O, the oxidation process is accompanied by the accumulation of reduced nicotinamide adenine dinucleotide phosphate (NADPH), an important co-enzyme. It also carries non-oxidative steps to convert into ribose 5 phosphate (6 carbon sugar to 5 carbon sugar). The activity of the pathway is normally regulated by glutathione (an antioxidant) and by insulin and other hormones that affect glucose metabolism.

All of the above bio-chemical processes need a series of co-enzymes, some need vitamins and some need minerals as co-factors. Each of the co-enzymes carries their unique functionality and lack of such co-enzymes cause impairment to energy production. During these bio-chemical reactions, waste or toxic substance may be produced which should be eliminated as cellular respiration. The energy produced should be transferred and during energy transport system ROS molecules are produced which may need to be neutralized by the cell as it produces. These are constant processes, minute to minute, day after day, 24 seven. The adequate co-enzymes, co-factors and antioxidants are in constant need to keep cellular functionally without having any stressful effect. In diabetic conditions all cells are stressed and balanced nutrients, vitamins, minerals, and antioxidants are definitely helpful.

Vitamins and minerals are often involved in the metabolic bio-chemicals process where enzymatic catalytic reactions are assisted as smooth processes of co-enzymes and co-factors. Enzymes are required for all metabolic reactions. Co-enzymes, co-factors are molecules that combine with an enzyme to facilitate enzyme functions. Co-factors stabilize the enzyme or substrate and assist directly in the reaction process. To mention a few; B-vitamins like thiamine(B1), riboflavin(B2), niacin(B3), pyridoxine(B6), folic acid, cyanocobalamine(B12), panothenic acid, biotin etc are important for energy metabolism.

• Thiamine--a portion of co-enzyme TTP, which convert pyruvate to Acetyl CoA. Thiamine phosphate is a co-enzyme required for carbohydrate metabolism. It also helps in the production of achetylcholine.
• Riboflavin—helps build the co-enzymes used in the process of cell respiration, such as FAD. It is a part of co-enzymes involved in the oxidation-reduction reactions. It is a part of antioxidant enzyme glutathione peroxidase.
• Niacin—it is a part of the energy transport molecules known as NAD and NADP. Co-enzymes assisting with glucose metabolism.
• B-6 group—pyridoxal, pyridoxine, and pyridoxmine; part of co-enzymes for more than 100 enzymes in amino acid metabolism.
• Folic acid—is a co-enzyme in the process of making various nucleic acid maintains cell's integrity.
• Pantothenic acid—main part of the structure of the enzyme CoA in the process of cell respiration.
• Biotin—Co₂ carrier in the Kreb-cycle (glucose metabolism). It is a link to the process of gluconeogenesis.
• All other vitamins and their individual functions also work as antioxidants. In addition to the vitamins, other molecules like alpha-lipoic acid, l-carnitine, glutathione,e etc are equally important to have in the body to detoxify the ROS as it is produced.
• Magnesium—is a co-factor of at least 300 enzymes of the enzyme system.
• Copper, Zinc, and Manganese all act as co-factors of many enzymes of the enzyme system.

Sugar metabolism is so important that certain cells like brain cells and blood cells only use glucose as an energy source and glucose entrance of these cells are independent of insulin. Most of the body cells are insulin dependent for glucose entrance. That's why insulin secretion is as vital, as it is needed in the first step of glucose utilization by the cell. Lack of insulin availability or insulin resistance glucose molecules fail to enter inside the cell; causes blood glucose rise; and over the period the condition become a pathogenesis of multiple health problems. During hyperglycemia, where cells use " insulin independent pathways" there will be excess glucose inside the cells causing toxicity and where cells follow " insulin dependent pathways " will have less glucose inside causing less energy production and the cell becomes dysfunctional. These suggest that as time passes, the cells of people with diabetes are more and more dysfunctional and require more and more medications. However, these oral medications offer time limited functionality either by enhancing or inhibiting bio-chemical processes, pathways and or physicochemical pathways as follows:

• Reduce GI glucose absorption/stimulate insulin release/reduce glucagon release (inducing GLP-1/GIP pathways by inhibiting DPP4),
• Directly blocking K_ATP channel in the pancreatic ß-cell membrane and inducing Ca²⁺ influx to trigger insulin release
• Directly blocking Gluconeogenesis pathways to reduce glucose syntheses.
• Decreasing re-absorption process of glucose through kidneys where it excreted in the urine decreasing the blood glucose

All of these medications are time limiting functions that address sugar control and do not necessarily correct dysfunctional body cells, be pancreatic, or any other body cells. However, the body needs energy every minute of every day, 24 seven, and attention should be given on how to correct the dysfunctional pancreatic ß-cell first, which will improve glucose metabolism for energy production, which in-turn improves all other cells functionality, slowly and surely while taking of vitamins, micronutrients, and antioxidants on a regular basis.

Diabetes induced complications:

People living with diabetes may have to deal with short-term or long-term complications as a result of their conditions.

1. Short-term complications include hypoglycemia, diabetic ketoacidosis (DKA), and hyperosmolar hyperglycemic state (HHS).
2. Long-term complications include how diabetes affects eye (retinopathy), heart (cardiovascular disease), kidneys (nephropathy), and nerves and feet (neuropathy)
3. Symptoms of hypoglycemia (low sugar) include sweating, feeling shaky, tiredness, blurred vision, lack of concentration, headache, going pale etc.
4. Symptoms of hyperglycemia (high sugar) include increased urination, thirst, hunger, nausea etc.

Diabetic Ketoacidosis: In diabetes when the sugar cannot get into the cells, it stays in the blood. The kidney filters some and excrete through urine. Because the cells cannot receive the sugar for energy, it begins to break fats and proteins for energy, resulting ketones/fatty acids in the blood stream, causing metabolic acidosis, called diabetic ketiacidosis – a condition that could lead to life threatening complications.

Note: Diabetic ketoacidosis arises because lack of insulin in the body to begin with. This leads elevation of glucagon to make available more glucose from glycogen (stored in liver) and also producing glucose from fatty acid, lactaid following gluconeogenesis – bringing even more glucose into blood stream and worsening the condition – more and more medication is required including insulin therapy.

Polyol Pathway: When there is excess glucose where cell cannot utilize in normal metabolic energy production process, part of the glucose may transformed into sorbitol following polyol pathways. The sorbitol is unable to pass cell membrane, and deposition of these molecules can cause osmotic pressure leading micro vascular problem especially, nerve, kidneys and eyes.

Diabetes induced complications pathways: It has been shown that more ROS are produced in various tissues under diabetic conditions. As a result of increased ROS in cells, more complications may arise.

• Increased advanced glycetion end products causes vascular problems that lead to cardiac issues and peripheral circulation issues that can affect nerve endings. These conditions can be pathways towards heart attack, peripheral vascular disease, gangrene, nerve ending pains, eye complications etc.
• The ROS accumulation in mitochondria reacts with mtDNA and may cause mtDNA mutations that could lead to cell proliferations, cell death, chronic inflammation, cancer and many other diseases.
• Atherosclerosis and cardio-myopathy in diabetes are caused in part by pathway-selective insulin resistance.

Be positive; be aware of the comprehensive glucose metabolism process that includes:

1. Glucose absorption and transport systems, • Energy production pathways, • Energy transport pathways,
2. Cellular stressed level due to ROS and other toxic waste • Inter-cellular respiratory system and
3. The body's regular glucose homeostasis process, etc.

The necessity of nutrients, co-enzymes, vitamins, minerals, and antioxidants are inevitable, every minute, every day, 24 seven.

The supplementation of such balanced nutrients supplied by ADH will definitely benefit not only the diabetes population, but also the pre-diabetic.

Use HEALTHY-BETIC^TM product lines REGULARLY to manage your blood sugar level as well as other diabetes-induced complications that you may be experiencing.

Metabolism of common monosaccharides, including glycolysis, gluconeogenesis, glycogenesis and glycogenolysis