Question

a. Is his current therapy working? (350 words) (20 marks)

Justify your answer by using the evidence presented in the case study.

In your answer, you should also explain the pathophysiology of any of the signs/symptoms observed.

Present universal guidelines for diabetes mellitus type 2 (T2D) management encourage preliminary changes in lifestyle (i.e., exercise and diet). Metformin is favored and prescribed as a first-line anti-diabetes treatment for diagnosed individuals who do not show contraindications to the drug. After commencing this treatment, patients glycemic targets ought to be assessed after three to six months. For suboptimal blood glucose level control (target glycated hemoglobin [HbA1c]) (Laiteerapong et al., 2019), dual combination treatment is commenced. This, or other subsequent treatment modifications, must be followed by another test of glycemic targets three months later, and regularly after that, for ascertaining whether or not therapeutic goals for the patient are being accomplished, and whether there is a need for further alteration or intensification of treatment (Davies et al., 2018).

Gliclazide can improve beta-cell results as well, when compared with other sulfonylureas, suggested by increased duration before the need for insulin therapy commencement as against treatment with glibenclamide (mean time from diabetes onset in case of gliclazide treatment: 27.7 years; 95% CI: 24.730.7; mean time in case of glibenclamide: 21.4 years; 95% CI: 18.724.2; p<0.001). Considering metformin improves insulin sensitivity as well as decreases basal production of liver glucose, and gliclazide stimulates insulin secretion, a clinical rationale exists for using combination treatment, considering their complementary action (Gottwald-Hostalek et al., 2016).

T2D represents a complicated cardiovascular/metabolic disorder accompanied by several pathophysiologic abnormalities, with the key abnormalities being ?-cell malfunction and liver/muscle insulin resistance. The former happens prematurely in T2Ds natural history and has now been recognized to be a more serious issue than considered earlier. Upper tertile IGT (impaired glucose tolerance) patients are almost maximally or maximally resistant to insulin, losing over 80 percent of ?-cell functioning. Besides ?-cells, muscle, and liver (triumvirate), GI tract (incretin resistance/deficiency), adipocytes (quicker lipolysis), brain (neurotransmitter dysregulation and insulin resistance), ?-cells (hyperglucagonemia), and kidney (greater glucose reabsorption) contribute significantly to glucose intolerance among those diagnosed with T2D. The above eight factors together are termed the ominous octet, dictating that1) there is a need for several drugs combined for correcting associated numerous pathophysiological abnormalities,2) therapy is grounded in known pathogenic defect reversal and not mere HbA1c reduction, and3) timely treatment commencement will retard or prevent progressive failure of ?-cells well-established among IGT patients (DeFronzo et al., 2013).

b. Look at Mr. Keens laboratory results. Which results should we be concerned about, and why? (200 words) (15 marks)

The blood pressure levels recorded for Mr. Keen are 162/85, suggesting Stage 2 Hypertension. (Stage 2 Hypertension is characterized by blood pressure levels of 160-179 / 100-109). Further, Mr. Keens HbA1c levels are 9.2%; the goal normally set by physicians for those diagnosed with both type 2 and type 1 diabetes is maintaining HbA1c levels below 7%, as maintenance of this level of HbA1c has been proven to retard the onset of diabetes-related complications among patients. Mr. Keens hyperglycemia levels must be monitored, as they stand at >140 mg/dl (7.8 mmol/l). Fasting blood sugar levels of 11.8 mmol/L in the patient, with a prior diabetes diagnosis, has been linked to a greater risk of mortality and complications (Corsino et al., 2017).

c. Why does insulin therapy lead to weight gain, and why would this be problematic for a patient with diabetes? (200 words) (15 marks)

Type 2 diabetics on insulin therapy gain weight, a tendency apparent in insulin-nave patients commencing insulin treatment as well as insulin users are intensifying treatment due to having poor glycemic control. The above phenomenon is extensively recorded and described. The chief weight gain related risk factor among insulin-administered patients is HbA1c or average blood sugar levels before insulin therapy commencement. Higher pre-treatment HbA1c level implies greater pre-treatment glycosuria and, consequently, more weight gain following treatment commencement. Roughly 12 months after commencing insulin therapy, insulin dosage begins to influence weight gain to some extent. However, it is found to be roughly four times less influential as compared to pre-therapy...

c. Mr. Keen should stop taking propranolol and commence valsartan 80mg/day.

The use of ?-blockers among type 2 diabetics and those with established CV (cardiovascular) risk factors have been linked to elevated risks of serious hypoglycemia and CV events. Propranolol and other ?-blockers might work protectively through lowering acute hypertension, CV events, and hypoglycemia-linked cardiac arrhythmias. But ?-blockers in themselves have the potential to increase acute hypoglycemia risks. Moreover, they can dampen initial warning signs, resulting in hypoglycemia unawareness, besides causing weight gain that can, with time, exacerbate CV event risk. Valsartan might be prescribed/administered along with other medications for heart failure. But the triple-drug combination of a mineralocorticoid receptor antagonist /? -blocker, ACE inhibitor, and valsartan is discouraged (Hackethal, 2018).

d. Mr. Keen should stop taking corticosteroids and instead start taking methotrexate 15mg once a week.

As Mr. Keen suffers from T2D, continued corticosteroid usage will probably result in increased blood sugar levels. In the case of a significant increase in blood sugar levels, Mr. Keen may have to modify or increase his medication to achieve optimal levels. MTX or methotrexate is an extraordinary medicine with an important role in managing RA (rheumatoid arthritis) at all stages of evolution. Some of its positive quaities are great general efficacy for symptoms and signs, inhibited structural harm, and function preservation with controllable and acceptable safety, yet-to-be-rivaled cost-efficacy, a large dosage-titratable range, and options for administering either parenterally or orally (Taylor et al., 2019).

e. Mr. Keen should stop taking St Johns Wort and instead seek psychotherapy for his depression.

St. Johns Wort possesses a hyperforin element, a separate part of its phytochemical and molecular structure, inducing CYP3A4. Also, the medication is a PXR (pregnane X receptor) agonist, which activates the p-glycoprotein and PXR receptor, besides modifying the pharmacokinetics of several other drugs. This point must be borne in mind as roughly three in ten liver-metabolized medications are dependent on this PRX receptor (Wick, 2016). Another efficient therapy is psychotherapy, alone, or combined with medications. Its benefits include a lasting impact that safeguards…