RECENT RECOMMENDATIONS IN THERAPEUTIC APPROACHES FOR DIABETES AND ITS COMORBIDITIES

RECENT RECOMMENDATIONS IN THERAPEUTIC APPROACHES FOR DIABETES AND ITS COMORBIDITIES

Gulnaazbanu. M. Shaikh * and Jagdish Kakadiya

Department of Pharmacology, Parul Institute of Pharmacy & Research, Limda, Waghodia, Vadodara, Gujarat, India.

ABSTRACT: Diabetes Mellitus (DM) is a persistent metabolic cluster of diseases that involves erroneously excessive blood glucose levels. The polygenic disorder cluster of diseases includes Type I, Type II, Physiological state polygenic disorder (Gestational diabetes), Infant polygenic disorder (Neonatal diabetes), Maturity Onset Diabetes of the Young (MODY), and secondary causes because of endocrinopathies, steroid use and-so-on. Type I and Type II are the principal subtypes of DM, which are classically consequences of defective insulin secretion (Type I Diabetes Mellitus-TIDM) and /or action (Type II Diabetes Mellitus-TIIDM). TIDM likely gets access in kids or adolescents, whereas TIIDM impacts middle elderly and older adults who've extended hyperglycemia because of a bad way of life, lack of exercise, and nutritional choices. There is a vital distinction between TIDM and TIIDM, and consequently, every kind has diverse aetiologies, treatments, and medical presentations. This review article provides acquired facts regarding recently recommended guidelines for diabetes and its complications.

Keywords: Diabetes, TIIDM, Hyperglycaemia, Dyslipidaemia, Antihyperglycemic Treatment

INTRODUCTION: A historic assessment manifests that the word "Diabetes" was initially utilized by Apollonius of Memphis around 250-300 BC. Though "Diabetes mellitus" word abstracted from the Greek phrase siphon, which implies - to pass through, and the Latin phrase Mellitus, which means candy so, the sugary nature of excrement was determined through Egyptian, Indian, and Ancient Greek civilizations. Therefore the proliferation of the phrase Diabetes Mellitus came into being.

The major feature of the pancreatic gland within the pathophysiology of diabetes became recognized in 1889 by Hermann Minkowski and Mering. By the exploitation of that conclusion, Banting et al. purified the secretion of hormone Insulin from the pancreatic gland on the cows at the University of Toronto, Canada; resulting in the provision of a successful treatment for diabetes in 1922 ¹. Furtherly, it is concluded that the significant upsurge in blood sugar level due to insulin’s insufficiency to action results in TIIDM.

Therefore, hyperglycemia is the foremost reason for diabetes and comorbidities, such as coronary artery disease (CAD), cardiovascular disease (CVD), nephropathy, neuropathy, and retinopathy ². Multiple findings, in addition to control strategies, have been created over the years to conquer this developing problem. Woefully, even today, diabetes is one of the foremost common persistent illnesses within the US nation and worldwide. In 2019, diabetes became the 9^th major common count of dying with the expected range of 1.5 million immediately springing up through diabetes and in the US; its leftovers are the 7^th fundamental risk disorder to life according to WHO. Type 2 diabetes mellitus (T2DM) has reached epidemic proportions worldwide, posing a growing public health threat. In wealthy nations, the prevalence of TIIDM varies from 6.9% to 10.2%, whereas it exceeds 7% in growing ones ^3-4. CVD is responsible for 17.5 million fatalities per year, approximately 31% of all mortality globally ⁵. A rising amount of research demonstrates that TIIDM, CVD, and HT (Hypertension) have significant interaction. To begin with, TIIDM is well-known as a key risk factor ⁶. Likely to microvascular complications such as nephropathy, neuropathy, and retinopathy, TIIDM is a likelihood with macrovascular complications (CVD, peripheral artery disease, and cerebrovascular disease). Another eye-catching factor is almost individuals have obesity as a primary alternative risk factor for TIIDM ^7-16. Kind of Diabetes mentioned in ensuing paragraphs.

Classification:

1. TIDM (Type I Diabetes Mellitus): It is the most typical kind of polygenic disorder in youth. TIDM (due to autoimmune β cell destruction, usually leading to absolute insulin deficiency, including latent autoimmune diabetes of adulthood) is taken into consideration for 5-10% of DM and is characterized by response pathology of autoimmune disorder of pancreatic islets, conjointly known as islets of Langerhans (the organization of cells) and its consequences deficiency of insulin within the body. The explanation behind this autoimmunity could be a mixture of genetic vulnerability and environmental elements such as viral infection, toxins, life vogue, or various nutritional elements incriminated as triggers. Type I Diabetes Mellitus is likely visible in youngsters and teenagers though it may be developed at any age ¹⁷. An associative squad of experts trained in paediatric special DM management and perceptive to the provocation of kids and youth with TIDM and their families. Furthermore, the distinctive aspects of medical specialty TIDM management ought to offer to look after this populace. Youngsters with TIDM are usually diagnosed with excessive urination/ thirst, and around partly half with diabetic ketoacidosis (DKA). Adults with TIDM might not represent typical featured and should have a brief absolution from the requirement for internal secretion- Insulin. The determination could become a lot conspicuous over the grace period and may be reconceived if there's any consideration ^17-18.

2. TIIDM (Type II Diabetes Mellitus): Authentic data shows that TIIDM in adolescents has been prolonged 20 years a foretime and modern assessment shows an event approximate five thousand current incidents in a year in the United States. TIIDM is thought about as around ninetieth percent of the instances of diabetes. Insulin resistance is outlined because of a reaction to declined insulin. In this state of scenario, insulin is unproductive and is at terribly begin contrastingly upraised in insulin secretion production to keep up aldohexose homeostasis; however as time passes, insulin secretion production drops, ensuing in TIIDM ^17-18.

TIIDM is maximum likely visible in center elderly individuals i.e. older than forty-five years. However, it's far visible in children, adolescents, and more youthful adults because of the leap of obesity, lazy way of life, and vitality-dense diets ¹⁸.

3. Gestational Diabetes (Physiological State Polygenic Disorder) Mellitus: In a child-bearing situation, firstly detected hyperglycemia, is assessed because the class underneath Gestational Diabetes Mellitus (GDM) is conjointly referred to as excessive blood glucose degree for the duration of being pregnant. It may arise anytime in the course of gestation, which is typical impacts at some point in 2nd and 3rd trimesters in pregnant ladies. According to the American Diabetes Association (ADA), GDM includes 7% of all pregnancies. It is understood that ladies with progeny cells and GDM have a maximum chance of occurring TIIDM within further life. Hypertension, Preeclampsia/ toxemia, and hydramnios make GDM elaborated and might resulting an increment in operative interventions. The possibilities of gain in weight and size (macrosomia) or congenital malformation may also evolve in the fetus. Still, after the patter of tiny toes, any such newborn may also have respiration misery syndrome and consequent youth and adolescent obesity. The ancient overview suggests that congenital anomalies in preceding child or after delivery, obesity, older age, enormous gestational weight gain, or genetic records of DM are probability threat elements for GDM ^17-18.

4. Secondary/ Monogenic Diabetes Syndrome: This kind of diabetes happens once while one genetic alteration ensues in an autosomal dominant gene. Infant DM (Neonatal diabetes) and Maturity Onset Diabetes of the Young (MODY) are instances of Monogenetic Diabetes. Patients below the age of 25 years have the probability of hereditary disease MODY, and approximately 1-5% of all Diabetes instances are because of Inheritable diabetes. Hormone secretion disturbances (ex., Harvey Williams Cushing syndrome), the complexity of different disorder that influences the pancreas gland (ex., pancreatitis), or pills like Corticosteroids may also lead to secondary diabetes. Provisioners must grasp that classification of polygenic disorder diet isn't perpetually clear-cut at presentation; miss-representation could occur ^17-18.

Pathophysiology: Pathophysiology of diabetes is related to the extent of insulin in the body and the body's capacity to make use of insulin. Internal secretion- Insulin function is the compost out-turn of plasma Insulin concentration (assured by beta cell action) and Insulin reactivity of primarily focused tissues (hepatic, skeletal muscle, and fat tissue). These sites of the ordinance are all harmed to fluid extents in patients with TIIDM. The aetiologia of TIIDM contains a dominant genetic part. it's an inherited condition with a comparative 4-fold inflated risk of disorder for persons with a diabetic birth parent or relative, expanding to 6-fold if each folk has TIIDM. Though over twenty genetic cores with a clear correlation to TIIDM are known through the latest genome-wide alliance studies, the state of every is comparatively small ¹⁹. In TIDM, there may be a complete loss of insulin, while in TIIDM diabetes; the peripheral tissues resist the consequences of insulin. Generally, the insulin-freeing manner is carried out through pancreatic beta cells because of the higher concentration stage of blood glucose. Glucose is constantly required through the brain for regular functions to occur. Low blood glucose degree or Hypoglycemia is generally consequencing of the insulin and oral antihyperglycemic pills used to remedy diabetes.

To gather strength reserves, the pathophysiology of diabetes requires plasma concentrations of glucose signaling the vital nervous system, based on the blood float to cerebral part, arterial blood glucose, tissue restore processes, the charge of velocity that blood glucose concentration fall and different from being had metabolic fuels ⁵. Hypoglycemia triggered an upsurge in autonomic action to the prognosis of low blood sugar glucose degree required glucose consumption as an instant remedy. This is in reaction to hypoglycemia effects in decreased insulin secretion, raised in glucose counter-regulatory hormones like glucagon as endocrine and epinephrine as a vasoconstrictor, a more reaction of the sympathetic nervous system and adrenal medulla, associated signs and symptoms, and finally, Neuro-Cognitive Disorders (NCDs), seizures or coma.

The interplay of Insulin, Glucagon, and Growth Hormones with hepatic capabilities and their involvement in kidney characteristics make the anatomical mechanisms of this disorder difficult to decide and widely various among patients ^20-21. The state is best considered a miscellaneous condition of abnormally regulated aldohexose metabolism related to impaired hypoglycemic agent secretion and action. Morbidly obesity or fleshiness may be a common correlation of TIIDM in approximately 80% of affected people. There's no clear challenging occurrence for most persons developing TIIDM; rather, the situation is assumed to develop bit by bit over the years with progression through recognizable prediabetic stages. TIIDM results once there's inadequate insulin function to keep plasma aldohexose levels in the optimum vary ^20-22-23. More complete evaluations of the pathophysiology of diabetes were discovered on internet sites in addition to journals of ADA (American Diabetes Association) and scientific texts.

Sign-symptoms:

Persistent signs of diabetes involve:

1. Frequent dehydration
2. Often should move for urine
3. Tiredness
4. Hungry - even though overeating
5. Blurry vision
6. Healing manner of cuts getting gradually down
7. Weight loss (TIIDM)
8. Tingling, ache, or numbness in hands/feet

Although there are many similarities in Type I and Type II diabetes, the reason for everyone may vary, and the treatment is generally quite different, too. According to the American Diabetes Association (ADA), signs of TIDM onset in little one or at infant age are the younger kids who urine often, consume huge quantities, drop weight, and become increasingly more fatigued and ill. When the kids are recognized with diabetes occasionally, they may be having Diabetic Ketoacidosis (DKA). Ketones can know that while there may be a loss of insulin inside the human body, the body produces excessive ranges of H+ ions. Diabetic Ketoacidosis (DKA) is a clinical emergency that typically calls for instant care with insulin and IV fluids. When diabetes is recognized in an adult, they're frequently falsely advised that they've Type II diabetes. Due to perhaps lack of expertise through a few physicians, TIDM can begin at any age and in human beings of each form and size. Patients with having highest blood glucose TIDM and ordinary threat elements for Type II diabetes, including weight problems and bodily inactivity, are often misdiagnosed ¹⁷. If a person is recognized with Type II diabetes, however, now no longer responding nicely to the most common remedies for TIIDM, the worthwhile manner for them is to go to an endocrinologist to decide the sort of diabetes happening. The antibody assessments and range of C-peptide are needed in this type of condition. Gestational diabetes possibly has no signs, it's required for at-threat ladies to be examined at the right time throughout pregnancy ^18-24. So, their physicians can reveal raised blood glucose degree at an everyday visit and begins them on the diet, workout, and oral medications. The preliminary detection, diagnosis, and remedy of diabetes can lessen the chance of growing the complications of diabetes.

Standards of Care and Diagnosis Criteria: The Diagnostic criteria are shown in table 1.1. Marketed discrepancies between measured A1C and plasma aldohexose levels should prompt the thought that A1C assay might not be answerable for that individual. One ought to the thought of exploiting A1C assay while not interference or plasma glucose criteria for identification.¹⁸ Consideration of diabetes may be both via means of HbA1C (Hemoglobin A1C) standards or blood glucose concentration (fasting or 2 hours plasma glucose) ^17-18.

5. Fasting Blood/Plasma Glucose (FPG): After 8 hours in a single day fasting condition, a sample of blood is taken, and according to the American Diabetes Association (ADA), the Fasting Plasma Glucose (FPG) stage of ≥126 mg/dL (7.0 mm/L) is accordant with diagnosis.

FIG. 1: CRITERIA FOR THE SCREENING AND DIAGNOSIS OF PREDIABETES AND DIABETES. *For all three tests, the risk is continuous, extending below the lower limit of the range and becoming disproportionately greater at the higher end of the range. ± In the absence of unequivocal hyperglycemia, diagnosis requires two separate samples + Only diagnostic in a patient with classic symptoms of hyperglycaemic crisis ¹⁸

6. Two-hour Oral Glucose (Aldohexose) Tolerance Test (OGTT): The plasma glucose level is measured priors to and a couple of hours after the consumption of seventy-five gm of glucose on this test. If the PG (plasma glucose) degree is ≥200 mg/dL (11.1 mmol/L) in 2- an hour sample, Diabetes Mellitus (DM) is diagnosed. This OGITT is highly-priced than FPG, irrelevant, and has fundamental variability issues, with the pain of sufferers like they must at the least eat a food regimen with one hundred fifty g according to the day of carbohydrates for three to five days. With this, they're now recommended no longer to take any drug treatments that may affect glucose tolerance, along with thiazide, diuretics, and steroids ^17-18.

7. Glycated HbA1C: An avg. of plasma glucose over the two-three months may be detected through this test. Those affected persons having HbA1C greater than 6.5% (forty-eight mmol/mol) are recognized as having Diabetes Mellitus (DM) ^17-18. Due to pre-analytical variables, HbA1C is a greater convenient, quicker standardized test and indicates fewer variants and not an awful lot damaged through pressure or acute illness. For many patients, usually, HbA1C is having pricey and plenty of issues, along with decreased sensitivity. There is a way through which HbA1C ought to be measured: National Glycohemoglobin Standardization Program (NGSP) credential protocol to Diabetes Control and Complications Trial (DCCT) assay.

HbA1C is troubled through often situations including sickle cell thalassemia disorder condition, renal dialysis, pregnancy, blood loss or transfusion, or hematopoietic treatment so, it has now no longer been properly justified in non-white populations.¹⁷ The ferrous sulphate or cyanocobalamin deficiency offers an upward push to the assumed development of HbA1C, reducing its use in international locations with a higher incidence of anaemia ^17-18. Also, the relation between HbA1C and FPG is insignificant in kids and elderly patients. Testing has to be repeated later to diagnose DM if the individual is asymptomatic for all of the above tests. Now, sufferers with common signs and symptoms of excessive plasma sugar level (elevated starvation and thirst, more often urination), and random blood glucose greater than two hundred mg/dL are likewise enough to diagnose Diabetes Mellitus. The tests used for DM (FPG, OGTT with 75g for two hours PG HbA1C) are similarly proper, and there may be no compliance among the outcomes of those assessments ^17-18.

8. Diagnosis of Gestational Diabetes Mellitus: When the diabetes wasn't recognized to the pregnant ladies previously, this takes a look at what ought to be required at two to six months of pregnancy. To triumph over those conditions, the American Diabetes Association (ADA) and American College of Obstetrics (OB) and Gynecology (ACOG) endorse the use of both a one-step or two-step method for diagnosing GDM ^17-18.

One-step approach: After a single day of abstaining from food, 75 gm OGTT is carried out for DM, and blood samples are gathered for an hour and a pair of hours fasting. IF FPG attain of outreach 92 mg/L (5.1 mmol/L), 1-hour blood glucose of 180 mg/dL (10.0 mmol/L) or 2 hours serum glucose of 153 mg/dL (8.5 mmol/L), Gestational Diabetes Mellitus is diagnosed.

Two-step Approach:

• Step One: After having a meal, a 50 g glucose task test must be done. If plasma glucose is a hundred and forty mg/dL (7.8 mmol/L) more than or identical to, at 1 hour after the amount that may be carried at one time via way of means of a specified (referred to as load), then carry out step II.
• Step Two: After a long abstaining from food 100 gm OGTT is carried out. Average values of fasting is, plasma -glucose 95-105 mg/dL (5.5-5.8 mmol/L), 180-190 mg/dL (10.0-10.6 mmol/L) of one hour plasma glucose, 155-165 mg/dL (8.6-9.2 mmol/L) of two hour plasma glucose and 140-145 mg/dL (7.8-80mmol /L of three-hour plasma glucose. If two or greater than two plasma aldohexose levels equal or surpass those cutoffs, Gestational Diabetes Mellitus is diagnosed.

Contrast Diagnosis: Rather than TIDM, TIIDM, and MODY, there are numerous varieties of issues and/or illnesses having the corresponding signs and symptoms that get worse the pancreatic situation and outcomes in DM, including ^16-24:

When the reaction is provoked with the aid of using pills like;

• Glucocorticosteroid (a form of the anti-inflammatory drug).
• Neuroleptics (a form of anti-psychotic medications).
• Estradiol (a form of the hormonal drug).
• Antiprotozoals (like pentamidine mesylate) etc.
• Sulfonyluria

Diabetes is likewise related to several endocrinopathies like;

• Acromegaly (growth hormone),
• Cushing's syndrome (cortisol),
• Pheochromocytoma (epinephrine),
• Hypo/ Hyper Thyroidism (T3, T4)

Pancreatic system affecting situations like;

• Pancreatitis,
• Cystic fibrosis

The complexity of Ferric/Ferrous (bronzed diabetes) like;

• Hemochromatosis

Other including;

• Hereditary mutations in Langerhans cell activity and Humulin task,
• Syndrome 'X' (metabolic syndrome),
• Bacterial/ Viral/ Fungal Infection etc.

Pharmacological Interventions: The keystone of TIDM and TIIDM are dietary therapy and consumption of energy. Food with bad saturated fat, polished starch, rich polysaccharide glucose syrup, rich in fiber and oils should be restored.²⁵ Additionally, 90 to 150 min bodily health workout is beneficial to overweight person for slimming. Even though there is a variety of allopathic medicines designed for patients, it's a far reality that it has in no manner been accounted for that a person had recovered absolutely from diabetes. For pharmacological treatments and guidelines of ADA, see Fig. 2.

FIG. 2: PHARMACOLOGIC TREATMENT OF HYPERGLYCEMIA IN ADULTS WITH TYPE 2 DIABETES. CVOT, cardiovascular outcomes trial; DPP-4i, dipeptidyl peptidase 4 inhibitor; GLP-1 RA, glucagon-like peptide 1 receptor agonist; SGLT2i, sodium-glucose cotransporter 2 inhibitor; SU, sulfonylurea; TZD, thiazolidinedione ¹⁸

Metformin is used as a first earlier preference of treatment choices for patients of age 25-59 years with BMI ≥35 kg/m, higher fasting plasma glucose (e.g., ≥ 110 mg/dL), increased A1C (e.g., ≥ 6.0%), and in a female with prior GDM, if enough degree of blood sugar cannot be attained as much as the ideal degree. Apart from Metformin, there are various medicinal treatment plans like Glimepiride (Sulfonylurea), Sitagliptin (DPP-4 inhibitors), Incretin mimetic (GLP-1 receptor agonist), SGLT₂ (sodium-glucose co-transporter 2 inhibitors, alpha-glucosidase inhibitors and Humulin are applicable, as because long-term use of Metformin may cause vitamin B12 deficiency (diagnosed in Metformin treated patients); especially in patients with Anaemia or Peripheral neuropathy ^18-25. Modern studies have tested that the Empagliflozin as sodium-glucose co-transporter II (SGLT₂) inhibitors efficaciously enhance the glycemic manipulate by reducing the blood hemoglobin (HbA1C), glucose reducing triglycerides and cholesterol, reducing blood pressure, growing HDL, lowering hyperuricemia, adipose tissue or bodyweight and aerobic vascular mortality as well. Empagliflozin became the third agent inside the 'gliflozin' category authorized through each European Medicines Agency (EMA) and FDA in 2014, having the best selectivity for SGLT2 over SGLT1 (approx. 2700-fold); most of the SGLT2 inhibitors with inside the market. A continuous subcutaneous insulin catheter treatment procedure is rational for TIDM patients. The mortality state in DM is greater so, the SGLT₂, DPP4 inhibitors, and Metformin-like pills are the first preference of physicians to avoid/lessen the threat of cardiovascular dying.

FIG. 3: DRUG-SPECIFIC AND PATIENT FACTORS TO CONSIDER WHEN SELECTING ANTIHYPERGLYCEMIC TREATMENT IN ADULTS WITH TYPE 2 DIABETES. *For agent-specific recommendations, please refer to the manufacturer's prescribing information. †FDA-approved for CVD benefit. ‡FDA-approved for HF indication. §FDA-approved for CKD indication. CVOT, cardiovascular outcomes trial; DPP-4, dipeptidyl peptidase 4; GLP-1 RA, glucagon-like peptide 1 receptor agonist; NASH, non-alcoholic steatohepatitis; SQ, sub-cutaneous; T2D, type 2 diabetes ¹⁸

Although numerous pharmaceutical agents have been estimated for the prevention of Diabetes and Metformin has the strongest authentic evidence, there is no single agent approved by USFDA (U.S. Food and Drug Administration) ^18-26.

CONCLUSION: The level of HbA1C have to be much less than 7% and BP has to be much less than 130/85 mmHg with additively use of ACE (Angiotensin Converting Enzyme)/ ARB (Angiotensin- Receptor Blockers), to beat down the disorder of larger and medium-sized blood vessels (macrovascular disorder).

If we look out for fats deposition, the level of LDL-c has too much less than 100 mg/dL with an absence of ASCVD (Atherosclerotic Cardiovascular Disease) or much less than 70 mg/dL if ASCVD bearing. Physicians also recommend patients to perform toes check-ups as much as realizing toes scratches, which can be inconspicuous through reason of neuropathy; to conquer contamination in DM patients small dose ant depressive drugs, anti-epileptic drugs, and analgesics can be required. Pregabalin and Duloxetine are FDA-accredited drugs as a therapy of diabetic peripheral neuropathy. According to ADA, decreasing the dose of Aspirin moreover in favours of DM sufferers who're at increased endanger CV diseases; even though the act of decreasing CV complications of Aspirin in Diabetic patients has now no longer been clarified.

ACKNOWLEDGEMENT: To begin with, grateful to the Almighty for everything. I would like to express my deep gratitude to the Parul University, guide and supervisor; Dr. Jagdish Kakadiya and HOD; Dr. Snigdha Das Mandal, my principal; Dr. G. S. Chakraborty and all family members for their guidance, enthusiastic encouragement, and useful critiques of this work. Last but priorly, I especially wish to thank my parents and family for their support and encouragement throughout my study.

CONFLICTS OF INTEREST: There is no conflict of interest for this work.

REFERENCE:

1. Sapra A, Bhandari P and Wilhite Hughes A: Diabetes Mellitus StatPearls Publishing, Treasure Island 2021; 1-4.
2. Jagdish Kakadiya, Anteneh Tamirat, Utsav Shah, AnasJamsa, Snigdha Mandal and Shivkumar Rathod: Protective effect of Empagliflozin alone and its combination with metformin in experimentally induced MI in Diabetic Rats. Asian Journal of Phytomedicine and Clinical Research 2019; 7(2): 88-99.
3. Rajesh R and Patel Naren: SGLT-2 inhibitors A new sword for the treatment of T2DM. International Journal of Pharma Sciences and Research (IJPSR) 2010; 1(2): 139-147.
4. ESH/ESC Task Force for the Management of Arterial Hypertension. J Hypertens Guidelines 2013; 31(10): 1925–1938.
5. Jagdish Kakadiya: Overview of Cardiac Complication in Type 2 Diabetes and Recent Treatment - Saroglitazar. Inventi Rapid. Molecular Pharmacology 2014; (3): 1-4.
6. Shaw JE, Sicree RA and Zimmet PZ: Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract 2010; 87(1): 4–14.
7. World Health Organization (WHO). Cardiovascular disease. Accessed 15 Feb 2016.
8. Martin-Timon I, Sevillano-Collantes C and Segura-Galindo A: Type 2 diabetes and cardiovascular disease: have all risk factors the same strength? World J Diabetes 2014; 5(4): 444–470.
9. Aylsworth A, Dean Z and Van Norman C: Dapagliflozin for the treatment of type 2 diabetes mellitus. Ann Pharmacother 2014; 48(9): 1202–1208.
10. Jagdish Kakadiya and Nehal Shah: Glucose as a cardiovascular complication - Overview. Pharmacologyonline 2010; 1: 131-141.
11. Jagdish Kakadiya and Nehal Shah: Involvement of free radicals in cardiovascular complication in type 2 diabetes - A review. Pharmacologyonline 2009; 3: 862-886.
12. Kakadiya J, Mulani H and Shah N: Protective effect of hesperidin on cardiovascular complication in experimentally induced myocardial infarction in diabetes in rats. Journal of Basic and Clinical Pharmacy 2010; 1(2): 85.
13. Kakadiya J, Shah M and Shah NJ: Effect of nobivolol on serum diabetic marker and lipid profile in normal and streptozotocin-nicotinamide induced diabetic rats. Research Journal of Pharmaceutical Biological and Chemical Sciences 2010; 1(2): 329-34.
14. Kakadiya J, Mulani H and Shah N: Investigation effect of glimepiride on diabetic marker and cardiac lipid parameter in isoproterenol induced myocardial infarction in diabetes in rats. International Journal of Advances in Pharmaceutical Sciences 2010; 1(3): 1-6.
15. Jagdish K, Mehul S and Nehal S: Effect of hesperidin on serum glucose, hba1c and oxidative stress in myocardial tissue in experimentally induced myocardial infarction in diabetic rats. Pharmacognosy Journal 2010; 2(7): 185-9.
16. Kakadiya J and Shah N: Effect of hesperidin on cardiovascular complication in streptozotocin-nicotinamide induced type 2 diabetic rats. Int J Pharmacy Pharm Sci 2010; 2(3): 165-9.
17. Goyal A, Anastasopoulou C, Ngu M and Singh S: Hypocalcemia. Stat Pearls 2021; 1; 1-6.
18. American Diabetes Association; Standards of Medical Care in Diabetes 2022 Abridged for Primary Care Providers. Clin Diabetes, 2022; 40(1): 10–38.
19. Östenson CG: The pathophysiology of type 2 diabetes mellitus: an overview. Acta Physiologica Scandinavica. 2001; 171(3): 241-7.
20. Brunton LL, Chabner BA and Knollmann BC: Goodman & Gilman: the Pharmacological basis of therapeutics. McGraw hill 2019.
21. Moini J: Pathophysiology of diabetes. Epidemiology of Diabetes 2019; 30(1): 25-43.
22. Parveen N, Roy A and Prasad P: Diabetes Mellitus–pathophysiology & herbal management. Pharmaceutical and Biosciences Journal 2017; 34-42.
23. Reaven GM: Pathophysiology of insulin resistance in human disease. Physiological Reviews 1995; 75(3): 473-86.
24. Santiago JV: Overview of the complications of diabetes. Clinical Chemistry 1986; 32(10): 48-53.
25. Hussain S and Chowdhury TA: The impact of comorbidities on the pharmacological management of type 2 diabetes mellitus. Drugs 2019; 79(3): 231-42.
26. Patoulias D, Papadopoulos C, Stavropoulos K, Zografou I, Doumas M and Karagiannis A: Prognostic value of arterial stiffness measurements in cardiovascular disease, diabetes, and its complications: The potential role of sodium‐glucose co‐transporter‐2 inhibitors. The Journal of Clinical Hypertension 2020; 22(4): 562-71.
    

    ---

    How to cite this article:

    Shaikh GM and Kakadia J: Recent recommendations in therapeutic approaches for diabetes and its co-morbidities. Int J Pharm Sci & Res 2022; 13(11): 4401-09. doi: 10.13040/IJPSR.0975-8232.13(11).4401-09.

    ---

    All © 2022 are reserved by International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.