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How to Prevent, Treat, and Manage Type-2 Diabetes Mellitus?

Dr. Khalid is a physician, a researcher, a health writer, and holds a Ph.D. in clinical research.

Insulin and glucose production in type 2 diabetes: Insulin (green dots) is produced in the pancreas, and acts with glucose (blue dots) to regulate energy in the body's cells.

Insulin and glucose production in type 2 diabetes: Insulin (green dots) is produced in the pancreas, and acts with glucose (blue dots) to regulate energy in the body's cells.

What is Type-2 Diabetes Mellitus (T2DM)?

Diabetes mellitus is a chronic metabolic condition that progressively develops through the establishment of persistent hyperglycemia (Goyal & Jialal, 2020). Diabetes onset and development is the outcome of peripheral insulin resistance and insulin secretion impairment in the affected patients. The deterioration of multiple organ systems occurs under the impact of diabetes mellitus based on metabolic aberrations and chronic hyperglycemia. Some of the organ system complications of type-2 diabetes mellitus include microvascular manifestations, neuropathy, nephropathy, and retinopathy. The T2DM type-2 patients experience an increased risk of cardiovascular disease and related clinical complications. Almost 90% of diabetes cases are based on T2DM complications requiring systematic treatment through the blend of pharmacotherapy and lifestyle approaches (Goyal & Jialal, 2020). The onset of type-2 diabetes mellitus potentially elevates insulin resistance while delaying the physiological responses of the affected patients against insulin secretion. This initially increases insulin production for the optimization of glycemic control.

The maintenance of glucose homeostasis is paramount to the normal physiological functioning of the human body. The disruption of glucose homeostasis is initially followed by increased insulin secretion that diminishes over time, thereby increasing the health risk of T2DM patients. The individuals above 45 years of age experience an elevated risk for T2DM and related organ system complications (Goyal & Jialal, 2020). However, energy-dense diets, physical inactivity, and obesity are some of the commonly reported factors that substantially increase the risk of T2DM among younger adults, adolescents, and children. T2DM patients experience an elevated risk of premature death based on a range of long/short-term complications. The late recognition and insidious onset of T2DM are the preliminary causes of increased morbidity/mortality patterns in resource-limited regions of the world.

Diabetes (Key facts)

Diabetes (Key facts)

What is the Epidemiology of Type-2 Diabetes Mellitus (T2DM)?

Diabetes mellitus develops under the impact of insulin secretion insufficiency that leads to the impairment of protein/lipid/carbohydrate metabolisms and the establishment of chronic hyperglycemia (Wu, Ding, Tanaka, & Zhang, 2014). Pre-diabetes and diabetes reportedly impact 15.5% of Chinese youngsters. The simultaneous interaction between environmental, genetic, and lifestyle factors leads to the development of T2DM among high-risk populations. Furthermore, T2DM development reciprocates with glucagon secretion elevation, basal insulin secretion’s abnormal pulsatility, and reduction in insulin release (1st phase). T2DM patients do not often require exogenous insulin administration; however, such need arises following the total failure of oral hypoglycaemic agents and dietary modifications in maintaining the blood glucose level or glycemic control. The development of diabetes complications deteriorates the quality of life of the affected patients to an unprecedented level. T2DM substantially elevates the socioeconomic burden of diabetic patients based on an unprecedented elevation in their health care costs.

366 million individuals globally experienced T2DM and related clinical complications in the year of 2011 (Olokoba, Obateru, & Olokoba, 2012). 552 million people could experience T2DM until 2030 across the globe due to their inappropriate lifestyle and other health risk factors. Approximately, 80% of the T2DM patients reside across middle/low-income nations of the world. 4.6 million deaths from T2DM complications across the globe reportedly occurred in the year of 2011. The lifestyle-related and environmental risk factors potentially impact T2DM incidence across various geographical regions of the globe. Various research studies reveal the probable rise in T2DM cases in upcoming decades among adults within the age group of 45-64 years. The increased prevalence of T2DM cases across developing nations necessitates the requirement of implementing robust preventive measures based on lifestyle modifications.

Comparative prevalence of diabetes in adults (20-79 years) in countries with high prevalence (≥ 10%). Data extracted from International Diabetes Federation Diabetes Atlas, 6th ed, 2013.

Comparative prevalence of diabetes in adults (20-79 years) in countries with high prevalence (≥ 10%). Data extracted from International Diabetes Federation Diabetes Atlas, 6th ed, 2013.

What are the Symptoms of Type-2 Diabetes Mellitus (T2DM)?

T2DM has the potential to develop in the absence of noticeable symptoms. However, prolonged blood glucose elevation based on deterioration in glycemic control mechanisms lead to the development of the following symptoms (IQWiG, 2006).

  1. Dizziness or lightheadedness
  2. Nausea
  3. Listlessness
  4. Tiredness
  5. Frequent urination or increased urinary frequency
  6. Extreme thirst

Diabetic coma or extremely elevated blood glucose level potentially increases the risk of consciousness loss, drowsiness, and confusion. The insulin resistance in diabetic patients emanates under the impact of a secretory defect that leads to the development of insulin deficiency.

What is Prediabetes?

Prediabetes is a clinical condition that manifests with an abnormal elevation in blood glucose levels. Prediabetes indicates a reported disruption in glycemic control; which is not strong enough to substantiate the onset of diabetes mellitus (CDC, 2019). Approximately, 84 million individuals across the United States experience pre-diabetes without actually knowing about this condition. The glycemic control disruption under the impact of prediabetes appears reversible following the desired dietary modification, lifestyle changes, and treatment. The below-mentioned factors potentially increase the risk of prediabetes and related clinical complications (American_Medical_Association, 2015).

  1. Overweight status or obesity
  2. Age of 45 years or above
  3. Family history of T2DM
  4. Blood pressure elevation
  5. Reduced physical activity (less than 3-times per 7-days)
  6. History of gestational diabetes
  7. History of a birth scenario where neonate’s weight is found to be greater than 9-pounds

What are the Risk Factors for Type-2 Diabetes Mellitus (T2DM)?

The individuals exposed to the following conditions or habits experience an elevated risk of T2DM (IQWiG, 2006).

  1. Genetic predisposition
  2. Family history of diabetes mellitus
  3. Prolonged consumption of medications that potentially disrupt blood glucose metabolism
  4. Sugar-oriented, high-fat, and low-fiber diet
  5. Smoking
  6. Lack of physical exercise
  7. Overweight/obesity

The T2DM risk evaluation is based on affirming the following laboratory outcomes (American Diabetes Association, 2010).

  1. A1C level within the range of 5.7%-6.4%
  2. 2-hourly plasma glucose level range of 140mg/dl-199mg/dl or 7.8mm/l-11.0mm/l (reported during [OGTT] oral glucose tolerance test)
  3. Fasting plasma glucose range of 100mg/dl-125mg/dl or 5.6mmol/l-6.9mmol/l

What are the Clinical Methods to Diagnose Type-2 Diabetes Mellitus (T2DM)?

A routine check-up is the most common measure that the physicians deploy in diagnosing T2DM, particularly in scenarios where the patients report minor symptoms (IQWiG, 2006). The physicians require clinically correlating physical exam findings with blood glucose levels of the suspected patients for affirming/ruling out their diabetes mellitus. The laboratory assessment of blood glucose level (obtained before 1st meal) followed by the blood glucose evaluation throughout the day helps in diagnosing T2DM in suspected patients. HbA1C assessment helps in evaluating the aggregate blood glucose levels of the past 2-3 months. The laboratory assessment of urine also helps in affirming T2DM based on the detection of glucose (in urine). T2DM diagnosis warrants the laboratory affirmation of any of the following outcomes. However, A1C, FPG, and OGTT testing interventions are repeatedly required in the absence of hyperglycemia despite the occurrence of T2DM’s clinical symptoms (American Diabetes Association, 2010).

  1. A1C level equal to or above 6.5%
  2. Random plasma glucose level equal to or greater than 11.1mm/liter or 200mg/dl
  3. OGTT (oral glucose tolerance test)-based 2-hourly plasma glucose level of 11.1mm/litre (i.e. 200mg/dl) or above
  4. 8-hourly fasting plasma glucose (FPG) of 7.0 mmol/l (i.e. 126 mg/dl) or above

What is the Pathophysiology of Type-2 Diabetes Mellitus (T2DM)?

Beta-cell dysfunction and insulin resistance potentially restrict the secretion of insulin in T2DM patients (Kahn, Cooper, & Prato, 2014). The insulin-sensitive tissues and beta cells interact with each other through a feedback loop process. The disintegration of this feedback loop potentially disrupts the glucose maintenance level and homeostasis. The beta-cell stimulation and associated insulin release support the uptake of fatty acids, amino acids, and glucose by insulin-sensitive tissues in healthy individuals. The systematic functioning of humoral systems and the brain is highly warranted to define the insulin secretion requirement of islet cells. The elevated production of insulin by beta cells occurs under the impact of insulin resistance with the core objective of optimizing the glucose tolerance level. However, the gradual elevation of plasma glucose level occurs following the physiological insufficiency of beta cells in synthesizing insulin. The impaired glucose tolerance reciprocates with insulin resistance that substantially reduces beta-cell functionality, thereby increasing the blood glucose level beyond the normal limit. The beta-cell function deterioration predominantly occurs in older adults or individuals with 1st-degree relatives affected with DM. Furthermore, polycystic ovary syndrome also elevates the risk of beta-cell dysfunction and diabetes in women. T2DM is frequently reported among ethnic and racial populations following the inheritance of beta-cell dysfunction. Evidence-based clinical literature describes the following sequential processes associated with the development of T2DM (Kahn, Cooper, & Prato, 2014).

  1. Reduction in the functional capacity of insulin-sensitive tissues based on insulin resistance
  2. Induction of feedback loop mechanism that initially improves the insulin secretion functionality of beta cells for effectively optimizing the glucose tolerance level
  3. The gradual deterioration of beta-cell functionality due to insulin resistance leads to a marked reduction in insulin output
  4. The glucose tolerance impairment strengthens under the impact of blood glucose level elevation
  5. The development of hyperglycemia under the sustained impact of beta-cell dysfunction eventually leads to the establishment of T2DM

The genetic factors predominantly influence the disruption of beta-cells and the development of T2DM. The environmental factors interact with genes in a manner to increase the risk of obesity, insulin resistance, and T2DM (Kahn, Cooper, & Prato, 2014). The expression of genes (associated with body adiposity and abnormal beta-cell function) following their environmental interaction finally leads to the development of T2DM.

T2DM Pathogenesis

T2DM Pathogenesis

The molecular mechanism of insulin resistance

The molecular mechanism of insulin resistance

What are the Macrovascular/Microvascular Complications of Type-2 Diabetes Mellitus (T2DM)?

T2DM patients remain highly predisposed to the below-mentioned macrovascular/microvascular complications (Chawla, Chawla, & Jaggi, 2016).

1. Diabetic nephropathy develops under the sustained impact of the following conditions.

a. Induction of protein kinase C and other intracellular signaling molecules
b. Elevated production of AGE (advanced glycation end product)
c. Accumulation of ROS (reactive oxygen species)

2. Diabetic retinopathy develops under the impact of hypertension and hyperglycemia. Diabetic retinopathy potentially increases the risk of the following conditions in T2DM patients.

a. Generalized arterial narrowing
b. Retinal microvascular abnormalities
c. Clinical stroke

3. Diabetic neuropathy reciprocates with the magnitude and duration of hypoglycemia. The pathogenesis of diabetic neuropathy is based on the following processes.

a. Hyperglycemia-induced polyol pathway mechanisms
b. Injury from the advanced glycation end product
c. Oxidative stress enhancement

What are the Significant Ways to Prevent and Treat Type-2 Diabetes Mellitus (T2DM)?

The elevated compliance with the following steps is highly needed to reduce the risk of T2DM and related complications (Asif, 2014).

  1. Establishment of optimal blood glucose levels
  2. Enhancement of health-related quality of life
  3. Treatment, delay, and prevention of T2DM complications
  4. The accomplishment of energy demands based on the normal physiological requirements
  5. Optimization of blood lipid levels
  6. Elevated consumption of polysaccharides/starch-based diet containing potatoes, bread, beans, rice, and maize
  7. Avoidance of toffees, sweets, and soft drinks since they contain refined sugars including sucrose and glucose
  8. T2DM patients have the option to utilize non-nutritive sweeteners including aspartame, NutraSweet, saccharine, and canderel
  9. T2DM patients should elevate their consumption of polyunsaturated fats, including vegetable oils
  10. Reduced consumption of cholesterol and saturated fatty acids
  11. Reduced consumption of animal fat-based food items including egg yolk, lard, and butter
  12. Reduction in dietary salt
  13. The T2DM patients affected with diabetic nephropathy should not only restrict their salt intake but also restrain from consuming a high protein diet based on chicken, soybean, crayfish, crab, beans, meat, and fish
  14. Moderation in alcohol consumption and cessation of cigarette smoking are highly required to reduce the risk of T2DM
  15. Elevated consumption of custard, soya bean, and papaya (i.e. semi-solid diet) is recommended for those T2DM patients who encounter difficulty in consuming solid food items
  16. The consumption of three meals per day by the hypoglycaemic patients receiving sulfonylureas helps in maintaining their glycemic control
  17. The consumption of small meals in short spurts helps the T2DM patients to reduce the frequency of their post-pyramidal blood glucose peaks
  18. The drug therapy optimization for overweight T2DM patients warrants their weight reduction while limiting the intake of calories
  19. The T2DM patients should not consume animal products and comply with a vegan diet to reduce their intake of saturated fats
  20. The avoidance of animal diet is also necessary for T2DM patients to restrict the consumption of animal proteins for reducing their risk of calcium loss and kidney problems
  21. The consumption of high-fiber (i.e. 40gms per day) is recommended for T2DM patients to reduce their risk of cardiovascular complications
  22. The high-fiber diet for T2DM patients includes whole-meal, millets, oats, barley, fruits, vegetables, and beans
  23. The consumption of a balanced diet (based on ¼ vegetables, ¼ starch, and ¼ protein with every meal) is required to maintain the energy balance of the T2DM patients
  24. The consumption of three balanced meals with a six-hourly interval per day is recommended for accomplishing the T2DM patients’ energy demands
  25. T2DM patients should avoid consuming white sugar and white flour and prioritize their intake of food items associated with a lower glycemic index
  26. The blend of physical activity/exercise and the Mediterranean diet is highly recommended to enhance the glycemic control of the T2DM patients
  27. Reduction in sedentary behavior is highly necessary for improving the glycemic control of T2DM patients
  28. Vitamin D supplementation helps to maintain the blood glucose levels of healthy people while reducing their risk of T2DM
  29. The avoidance of processed/packaged food items including additives, refined grains, and vegetable oils helps to maintain the overall metabolism, health, and wellness of individuals while minimizing their risk of T2DM.
  30. The T2DM patients are allowed to consume the following items.
  • Tea (restricted intake)
  • Coffee (not more than 4-cups per day)
  • Low-calorie drinks
  • Vegetable salad
  • Peppers
  • Aubergine
  • Cucumber
  • Onions
  • Tomatoes
  • Green leafy vegetables

What is the Pharmacotherapy for Type-2 Diabetes Mellitus (T2DM)?

The preliminary treatment of T2DM is based on the following (approved) oral medications (Marín-Peñalver, Martín-Timón, Sevillano-Collantes, & Cañizo-Gómez, 2016).

1. Metformin requires administration with any of the following medicine types for effectively managing the blood glucose level of the T2DM patients.

a. iSGLT2 (sodium-glucose co-transporter 2 inhibitors)
b. iDPP4 (dipeptidyl-peptidase 4 inhibitors)
c. RA-GLP1 (glucagon-like peptide-1 receptor agonist)
d. TZD (thiazolidinediones)
e. Alpha-glucosidase inhibitors
f. Glinides
g. Sulfonylureas
h. Insulin

2. Alpha-glucosidase inhibitors reversibly restrict the activity of membrane-bound intestinal alpha-glucoside hydrolase enzymes. This eventually delays the process of digestion and carbohydrate absorption, thereby minimizing the intensity of postprandial hyperglycemia. The substantial decrease in postprandial triglycerides results in a marked reduction in blood glucose levels. The commonly utilized alpha-glucosidase inhibitors include voglibose, miglitol, and acarbose.

3. Insulin secretagogues (i.e. Meglitinides and sulfonylureas) facilitate the secretion of insulin through the induction of pancreatic beta cells. These drugs prove to be safe and effective treatment options for reducing the blood glucose levels of T2DM patients. Insulin secretagogues are utilized in patient care scenarios that restrict the administration of metformin. However, these drugs are contraindicated for the patients affected with chronic kidney disease due to their risk of hypoglycemia.

4. Thiazolidinediones (i.e. pioglitazone and rosiglitazone) act on the liver, adipose tissue, and muscle to minimize glucose production and elevate the utilization of glucose. This eventually increases the insulin sensitivity of T2DM patients. Thiazolidinediones also help in safeguarding the functionality of pancreatic beta cells for optimizing the blood glucose levels.

5. iDPP4 (Dipeptidyl peptidase-4) inhibitors include alogliptin, linagliptin, saxagliptin, vildagliptin, and sitagliptin. These medicines assist in achieving the following therapeutic targets.

a. Elevation in incretin hormones
b. Insulin secretion elevation
c. Inhibition of glucagon
d. Glucoregulatory enhancement
e. Enhancement in islet function
f. Enhancement in glycemic control

6. iSGLT2 (sodium-glucose co-transporter-2 inhibitor) decreases hyperglycemia while elevating the excretion of glucose and minimizing its renal reabsorption rate. The regular administration of these medicines leads to diuresis and glucosuria in T2DM patients. This eventually decreases their blood pressure and weight over the course of treatment. iSGLT2 drugs include empagliflozin, canagliflozin, and dapagliflozin.

The injectable antidiabetic therapy utilizes any of the following therapeutic agents (Marín-Peñalver, Martín-Timón, Sevillano-Collantes, & Cañizo-Gómez, 2016).

1. RA- glucagon-like peptide (GLP)-1 administration helps in improving the production of insulin. GLP-1 therapy minimizes food consumption through satiety enhancement and delays the gastric emptying process. GLP-1 therapy also reduces glucagon secretion while increasing the glucose-dependent secretion of insulin. GLP-1 therapy utilizes any of the following drugs based on therapeutic goals.

a. Exenatide
b. Exenatide LAR
c. Lixisenatide
d. Liraglutide
e. Albiglutide
f. Dulaglutide

2. Exogenous insulin administration potentially assists in establishing glycemic control through the systematic administration of any of the following formulations.

a. Rapid-acting insulins including glulisine/lispro and aspart
b. Ultra-long acting insulins based on glargine U-300 and degludec
c. Long-acting insulins including detemir and glargine

Antihyperglycemic Therapy in T2DM

Antihyperglycemic Therapy in T2DM

What is the Herbal Treatment for Type-2 Diabetes Mellitus (T2DM)?

Herbal medicines help in establishing glycemic control in T2DM patients based on the accomplishment of the below-mentioned therapeutic targets (Pang et al., 2019).

  1. Reduction in inflammation
  2. Enhancement in the body’s antioxidant mechanisms
  3. Regulation of blood lipid levels
  4. Apoptosis inhibition in islet secretory cells
  5. Reduction in insulin resistance
  6. Reduction in abnormal plasma glucose levels

Some of the globally recognized antidiabetic herbal drugs include the following. These drugs assist in establishing glycemic control in T2DM patients (Pang et al., 2019).

  1. Memecylon umbellatum
  2. Lycii Radicis Cortex
  3. Tinospora cordifolia
  4. Rhizoma coptidis
  5. Cinnamomum cassia
  6. Radix Salviae miltiorrhizae
  7. Radix Rehmanniae
  8. Panax ginseng
  9. Fructus corni
  10. Morus alba L
  11. Portulaca oleracea
  12. Rosa damascene
  13. Punica granatum
  14. Bambusa arundinacea
  15. Lactuca sativa Linn
  16. Pueraria lobata,
  17. Panax ginseng
  18. Rehmannia glutinosa
  19. Poncirus fructu,
  20. Dioscorea batatas Decaisne,
  21. Evodia officinalis
  22. Amomum cadamomum
  23. Acer pycnanthum
  24. Lodhrasavam
  25. Schizandra chinensis
  26. Psidium guajava L
  27. Ephedra sinica
  28. Ramulus euonymi
  29. Radix Rehmanniae preparata
  30. Angelica
  31. Scutellaria baicalensis
  32. Astragalus membranaceus


References

American Diabetes Association. (2010). Diagnosis and Classification of Diabetes Mellitus. Diabetes Care, 33(1), S62-S69. doi:10.2337/dc10-S062

American Medical Association. (2015, 03 12). Do you have prediabetes? Here are the signs. Retrieved from https://www.ama-assn.org/delivering-care/diabetes/do-you-have-prediabetes-here-are-signs

Asif, M. (2014). The prevention and control the type-2 diabetes by changing lifestyle and dietary pattern. Journal of Education and Health Promotion. doi:10.4103/2277-9531.127541

CDC. (2019, 08 12). Prevent Type 2 Diabetes. Retrieved from Can Type 2 Diabetes Be Prevented?: cdc.gov/diabetes/prevent-type-2/index.html

Chawla, A., Chawla, R., & Jaggi, S. (2016). Microvasular and macrovascular complications in diabetes mellitus: Distinct or continuum? Indian Journal of Endocrinology and Metabolism, 20(4), 546-551. doi:10.4103/2230-8210.183480

Goyal, R., & Jialal, I. (2020). Diabetes Mellitus Type 2. In StatPearls. Treasure Island (FL): StatPearls Publishing. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK513253/

IQWiG. (2006). Type 2 diabetes: Overview. In InformedHealth.org. Cologne, Germany: Institute for Quality and Efficiency in Health Care. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK279509/

Kahn, S. E., Cooper, M. E., & Prato, S. D. (2014). Pathophysiology and treatment of type-2 diabetes:; Perspectives on the past, present, and future. Lancet, 383(9922), 1068-1083. doi:10.1016/S0140-6736(13)62154-6

Marín-Peñalver, J. J., Martín-Timón, I., Sevillano-Collantes, C., & Cañizo-Gómez, F. J. (2016). Update on the treatment of type 2 diabetes mellitus. World Journal of Diabetes, 7(17), 354–395. doi:10.4239/wjd.v7.i17.354

Olokoba, A. B., Obateru, O. A., & Olokoba, L. B. (2012). Type 2 Diabetes Mellitus: A Review of Current Trends. Oman Medical Journal, 27(4), 269-273. doi:10.5001/omj.2012.68

Pang, G. M., Li, F. X., Yan, Y., Zhanng, Y., Kong, L. L., Zhu, P., . . . Lu, C. (2019). Herbal medicine in the treatment of patients with type 2 diabetes mellitus. Chinese Medical Journal, 132(1), 78-85. doi:10.1097/CM9.0000000000000006

Wu, Y., Ding, Y., Tanaka, Y., & Zhang, W. (2014). Risk Factors Contributing to Type 2 Diabetes and Recent Advances in the Treatment and Prevention. International Journal of Medical Sciences, 11(11), 1185-1200. doi:10.7150/ijms.10001

This content is for informational purposes only and does not substitute for formal and individualized diagnosis, prognosis, treatment, prescription, and/or dietary advice from a licensed medical professional. Do not stop or alter your current course of treatment. If pregnant or nursing, consult with a qualified provider on an individual basis. Seek immediate help if you are experiencing a medical emergency.

© 2020 Dr Khalid Rahman

Discussion

Dr Khalid Rahman (author) from India on February 15, 2020:

@Jaya Ma'am

Thanks for your valuable feedback.

Jaya on February 15, 2020:

Very informative article.thanks dr khalid