Diabetes Mellitus Lecture Notes PDF

# Diabetes Mellitus ## Pancreas * **Exocrine gland (by duct):** Supplying digestive enzymes to the duodenum to break down proteins, lipids, carbohydrates, and nucleic acids in food. * **Endocrine gland:** The islets of langerhans, 3% of the gland * **a-cells:** secrete glucagons. * **B-cel...

# Diabetes Mellitus ## Pancreas * **Exocrine gland (by duct):** Supplying digestive enzymes to the duodenum to break down proteins, lipids, carbohydrates, and nucleic acids in food. * **Endocrine gland:** The islets of langerhans, 3% of the gland * **a-cells:** secrete glucagons. * **B-cells:** secrete insulin to control blood sugar levels throughout the day. ## Diabetes Mellitus Diabetes mellitus is a group of metabolic disorders with one common manifestation - hyperglycemia. ### Symptoms of Diabetes * Always tired * Always hungry * Sexual Problems * Vaginal Infections * Numb or tingling hands or feet * Sudden weight loss * Always thirsty * Frequent urination * Wounds that won’t heal * Blurry vision ### Normal Blood Glucose Level * **Fasting:** 70-110 mg/ml * **After meal:** 120-170 mg/ml ### Chronic Hyperglycemia Causes Damage To: * Eyes * Kidneys * Nerves * Heart and blood vessels. ### It Results Either From: * Inadequate secretion of hormone insulin * Inadequate response of target cells to insulin * Or a combination of these factors ## Diabetes Complications * Diabetic nephropathy * Peripheral neuropathy * Diabetic foot * Stroke * Heart attack * Peripheral artery disease * Diabetic retinopathy * Glaucoma * Cataracts ## Testing * **Fasting Plasma Glucose Test (FPG):** (cheap, fast) * **Oral Glucose Tolerance Test (OGTT):** *tested for 2 hrs after glucose-rich drink* * **Glycated Hemoglobin tests A1C** ## Blood Test Levels for Diagnosis of Diabetes and Prediabetes | Diabetes | A1C (%) | Fasting Plasma Glucose (mg/dL) | Oral Glucose Tolerance Test (mg/dL) | |---|---|---|---| | Diabetes | 6.5 or above | 126 or above | 200 or above| | Prediabetes | 5.7 to 6.4 | 100 to 125 | 140 to 199 | | Normal | About 5 | 99 or below | 139 or below | ## Types of Diabetes * **Type 1** * **Gestational diabetes mellitus (GDM)** * **Type 2** ### Type 1 Diabetes * Previously known as insulin-dependent diabetes. * It is an auto-immune disease where the body's immune system destroys the insulin-producing beta cells in the pancreas. * It can appear at any age (mostly infants) although commonly under 40, and is triggered by environmental factors such as: viruses, diet or chemicals in people genetically predisposed. ### Type 2 Diabetes * It is previously known as non-insulin dependent diabetes. * It is the most common form of diabetes, affecting 85-90% of all people with the disease. * This type of diabetes, also known as late-onset diabetes, is characterized by: * Insulin resistance * Relative insulin deficiency. ### Treatment: People with type 1 diabetes must: * Inject themselves with insulin several times a day * Follow a careful diet * Follow exercise plan. ### The Disease is Strongly Genetic in Origin but Lifestyle Factors Such as: * Excess weight * Inactivity * High blood pressure * Poor diet Are major risk factors for its development. * Symptoms may not show for many years and, by the time they appear. * Significant problems may have developed. * People with type 2 diabetes are twice as likely to suffer cardiovascular disease. ### Type 2 Diabetes May Be Treated by: * Dietary changes * Exercise and tablets * Insulin injections may later be required. ### Gestational Diabetes Mellitus (GDM) * GDM, or carbohydrate intolerance, is first diagnosed during pregnancy through an oral glucose tolerance test. * Between 5.5 and 8.8% of pregnant women. * While the carbohydrate intolerance usually returns to normal after the birth, the mother has a significant risk of developing permanent diabetes. * Self-care and dietary changes are essential in treatment along with insulin injection. ## Major Strategies in Treatments of Type 2 Diabetes Include: * **Agents that increase the amount of insulin secreted by the pancreas.** * **Agents that increase the sensitivity of target organs to insulin.** * **Agents that decrease the rate at which glucose is absorbed from the gastro-intestinal tract.** ## Drug Discovery From Nature * **Galega officinalis (ساب الماعز):** $ NH_2NH $ * **Metformin:** $ NH_2NH $ ## Pterocarpus marsupium * Known as Indian Kino Tree (family Leguminosae). * It is native to India, Nepal, & Sri Lanka. * Parts used: heartwood, leaves, flowers * The plant listed in Ayurveda in treatment for diabetes. * Flavonoid, Stilbene, chalcones &(-)-epicatechin, extracted from the bark of this plant has been shown to prevent alloxan-induced beta cell damage in rats * Both epicatechin and a crude alcohol extract significantly lowered the blood glucose level. * The plant actually shown to regenerate functional pancreatic beta cells. * No other drug or natural agent has been shown to generate this activity. ## Karela, Bitter Melon, Balsam-Pear * **Momordica charantia Family:** Curcubitaceae * **Parts used:** Fruit, leaves. * It has been used extensively in folk medicine as a remedy for diabetes. * The blood sugar lowering action of the fresh juice or extract of the unripe fruit has been clearly established in both experimental and clinical studies ## Active Constituents * Momordicin I and momordicin II (cucurbiticin derivatives). * Cucurbiticin B. * Iron, sodium, vitamins. * Charantin * Insulin-like polypeptide (polypeptide-P); insulinomimetic. ## Charantin * Is a hypoglycaemic agent extracted by alcohol * Composed of mixed steroids that is more potent than the drug tolbutamide which is often used in the treatment of diabetes. * Also contains an insulin-like polypeptide (polypeptide-P) which lowers blood sugar levels when injected subcutaneously into type 1 diabetic patients. * The oral administration of 50-60 ml of the juice has shown good results in clinical trials. ## Reported Effects * Anthelmintic * Antimalarial * Antiviral * For weight loss. ## Side Effects * High doses of bitter melon juice can cause abdominal pain and diarrhea. * Small children or anyone with hypoglycemia should not take bitter melon, since this herb could theoretically trigger or worsen low blood sugar, or hypoglycemia. * Furthermore, diabetics taking hypoglycemic drugs or insulin should use bitter melon with caution, as it may potentiate the effectiveness of the drugs, leading to severe hypoglycemia. * The seed contain vicine, so can trigger symptoms of favism in susceptible individuals. * The plant use is contraindicated in pregnancy. ## Onion and Garlic * Onion (Allium cepa) and garlic (Allium sativium) family Liliaceae have significant blood sugar lowering action. ## Active Constituents * Allyl propyl disulphide (APDS) * Allicin * Flavonoids * Vitamins and selenium. ## Mechanism of Action: Allyl propyl disulphide (APDS) lowers blood glucose levels by competing with insulin for insulin-inactivating sites in the liver. This results in an increase of free serum insulin. ## Onion Effects * Affect hepatic metabolism of glucose. * And / or increase the release of insulin. * And/or prevent insulin destruction. * Lower lipid level (reduce cholesterol levels) * Inhibit platelet aggregation * Antihypertensive. * Thus both are recommended for diabetic patients. ## Side Effects and Warnings * Bad breath and body odor * Allergic reactions * Skin burns * Rash ## Side Effects and Warnings * Bleeding is a potentially serious side effect of garlic use including bleeding after surgery and spontaneous bleeding * Dizziness, increased sweating, headache, itching, fever, chills, asthma flares, and runny nose. ## Interactions with Drugs * Garlic may increase the risk of bleeding when taken with drugs that also increase the risk of bleeding. * Examples include: aspirin * Anticoagulants and anti-platelet drugs * Non-steroidal anti-inflammatory drug. * Caution is advised when using medications that may also lower blood sugar. ## Pueraria Lobata (Kudzu) * **Roots:** Primary part utilized due to the high content of isoflavones like puerarin. * **Leaves and Flowers:** Occasionally used but less common in diabetes-related applications. * **Isoflavones** (e.g., puerarin, daidzein, genistein) * **Puerarols** * **Coumarins and triterpenoids** ## Mechanism of Action: * **Antioxidant Activity:** Reduces oxidative stress and prevents B-cell damage. * **Glucose Metabolism Regulation:** Enhances insulin sensitivity via activation of AMPK. * **Anti-Inflammatory Effects:** Reduces pro-inflammatory cytokines like TNF-a and IL-6. * **a-Glucosidase Inhibition:** Slows carbohydrate breakdown, lowering postprandial glucose levels. * **Adipogenesis Modulation:** Improves lipid profiles and reduces fat accumulation. ## Dose: * **Root Extract (Standardized):** Isoflavones: 100-300 mg/day, divided into 2-3 doses. * **Crude Powder:** 5-10 g/day, prepared as a decoction or capsule form. * **Tincture (1:5 in 45% ethanol):** 2-4 mL, 2-3 times daily. * **Tea/Decoction:** 5-10 g of dried root boiled in 250-500 mL water for 10-15 minutes, consumed 1-2 times daily. ## Potential Adverse Effects: * Gastrointestinal discomfort (nausea, diarrhea). * Allergic reactions (rare). * Potential interactions with anticoagulants (increased bleeding risk). * Hormonal interference due to phytoestrogen activity (caution in hormone-sensitive conditions). ## Fenugreek * **Trigonella foenum-graecum, family Fabaceae.** * Experimental and clinical studies have demonstrated the antidiabetic properties of fenugreek seeds. * The active ingredient responsible for the antidiabetic properties of fenugreek is in the defatted portion of the seed that contains the alkaloid trigonelline, nicotinic acid and coumarin. ## Active Constituents * Trigonelline (N-methyl derivative of nicotinic acid) * Scopoletin (coumarin) * Fenugreekine (a steroidal saponin peptide ester). * 4-hydroxyisoleucine (amino acid). ## Medicinal Parts * Ripe, dried seeds. ## Mechanism of Action: * It stimulates insulin secretion by the pancreas. * It reduces insulin resistance through raising the sensitivity of receptors for insulin. * Slow down the absorption of carbohydrates, delay stomach emptiness. * Flavonoids are free radical scavengers, they prevent ß-cell destruction in insulin dependent diabetes mellitus (IDDM) ## Clinical Studies * Clinical studies showed no hepatic or renal or hematological gastro-intestinal problems. * Clinical trials give a good idea of its use in humans without side effects. * Contraindicated: during last trimester in pregnancy as it has oxytocin like effect So may lead to abortion ## Bilberry or Blueberry Leaves * **Vaccinium myrtillus family Ericaceae** * **Medicinal Parts:** Dried leaves, dried or fresh fruits. * A decoction of the leaves of the blueberry has a long history of folk use in the treatment of diabetes. * The compound myrtillin (anthocyanoside) is apparently the most active ingredient. * A single dose produce effects lasting several weeks. ## Blueberry Anthocyanosides * Blueberry anthocyanosides also increase capillary integrity, inhibit free-radical damage (antioxidant) and improve the tone of the vascular system. * In Europe, it is used as an anti-haemorrhagic agent in the treatment of eye diseases. May its extract lower the risk of some diabetic complications, such as diabetic cataracts and retinopathy. ## Ginseng * Ginseng is found in North America and in eastern Asia (mostly Korea, northeast China). * Panax ginseng and P. quinquefolius (Araliaceae), used as adaptogenic due to ginsenosides and panaxosides metabolites. * Asian ginseng is commonly used in traditional Chinese medicine to treat diabetes. ## Mode of Action * Enhance the release of insulin from the pancreas * Increase the number of insulin receptors. * It also has a direct blood sugar-lowering effect. * A recent study found that 200 mg of ginseng extract per day improved blood sugar control as well as energy levels in Type 2 diabetes. ## Stevia * Stevia rebaudiana family Compositae * A.C: steviol glycosides (mainly stevioside and rebaudioside), which have 250-300 times the sweetness of sugar * Zero calories * Non fermented. * Early reports suggested that stevia might have beneficial effects on glucose tolerance (and therefore potentially help with diabetes). * Even if stevia did not have direct antidiabetic effects, its use as a sweetener could reduce intake of sugars in such patients. ## Cinnamon * Cinnamon bark has insulin-like properties, which able to decrease levels of: * Blood glucose * Triglycerides * Cholesterol * **Important especially for:** *type 2 diabetes patients and gestational diabetes.* * Just 1/2 a teaspoon of cinnamon into the daily diet of a diabetics can significantly reduce blood glucose levels. * Cinnamon can be easily bought at any food shop in a convenient powdered form. Just add cinnamon to what ever you would eat normally. ## Olive Leaf * **Olea europea L. Fam. Oleaceae** * Alcohol-extract of olive leaves has been reported to increase insulin secretion in diabetic rats- but not in healthy rats. * The hypoglycaemic effects were higher when compared to glibenclamide. * Olive leaf is suggested to be useful in the prophylaxis in autoimmune diabetes. **WHY?** * Olive leaf, contain polyphenols such as: * Oleuropein * Hydroxy-tyrosol * It was observed to improve: cardiac, hepatic and metabolic parameters by decreasing inflammation and oxidative stress in high fat fed. ## Black Seed * **Nigella sativa seeds (family Ranunculaceae)** creates insulin-like effects that: * Increase glucose uptake in skeletal muscles and adipose tissue due to its thymoquinone content. * The seed extract and oil can be considered quite promising as a supportive care in diabetics. ## White Mulberry (التوت الأبيض) * **Morus alba L. fam. Moraceae** * White Mulberry leaf extract is used as a folkloric remedy for treatment of diabetes. * Morus alba leaves seem to possess potential complementary effect on glycemic control in diabetes ## Active Constituents * L-deoxynojirimycin, sodium, copper, GABA, phytosterol ## In Vivo Examination * In vivo examination proves its antioxidant capacity and the fact that it decreased postprandial blood glucose probably by preventing glucose absorption in intestine via inhibition of alpha glycosidase. ## Conclusion Phyotherapy It should be kept in mind that phytotherapy is not an alternative but a complementary and supportive treatment to the conventional diabetes therapy and should be accompanied by diet and exercise treatment.