Efficacy Of Intensive Therapy In Type 2 Diabetes Patients With Microalbuminuria – Research Analysis

Background and main theme

Explore one issue/theme that interests you from within the content of the Learning Guide Covering Themes 1 – 3. be mindful, when you critique an article you are not just summarising the text and re-stating what the author has said, you are analysing, interpreting and evaluating the text.

Choose one original research article that reflects the topic you have chosen. This article must be submitted with your paper. You are expected to refer to further readings to support/oppose your discussion.

Background and main theme: Type 2 DM is a complex disorder that gives rise to major complications in the long duration like hypertension, increased aggregation of platelets, microvascular damage and reduction in life expectancy (Inzucchi et al. 2015). Risk for cardiovascular disease (CVD) is greatly increased in patients with type 2 diabetes playing an important role in beginning of atherosclerosis (Look AHEAD Research Group 2013). Moreover, diabetic vascular disease is responsible for coronary artery disease (CAD), stroke and risk of heart failure. Although, many interventions and trial studies were performed earlier to recommend for multi-factorial treatment of type 2 DM, however, this disease still remains a major cause for mortality. In a study conducted by Harrison et al. (2014) the efficacy of intensive therapy was assessed in patients with type 2 DM. The results showed that after 6 year-study, there was treatment failure with high fasting glucose, systolic blood pressure and lower sensitivity to inclusion. Until recently, Gæde et al. (2016) conducted an original intervention of follow-up, randomized control trial of intensive therapy as compared to conventional treatment in patients with microalbuminuria and type 2 diabetes for 7.8 years. The author was aimed at studying the potential of long-term, multi-factorial and intensified intervention in addressing the median differences in patients’ lifespan without or with cardiovascular events, which is considered a major risk in patients with type 2 diabetes and microalbuminuria. Intensive therapy (both pharmacological and behavioural approaches) is the main strategy that is discussed in the paper. The author hypothesized that intensive therapy would help in terms of gained disease free years of life from the cardiovascular events as major complications in patients with type 2 DM and microalbuminuria. The term “gained years of life” was emphasized in context to decrease in life expectancy among patients with type 2 DM and microalbuminuria.

Methodology: Gæde et al. (2016) adopted randomized controlled trial study design for their study. Patients were randomized 1:1 that were stratified in blocks by age, sex, urinary albumin excretion rate and diabetes duration using sealed envelopes (100 mg/day) in receiving conventional multi-factorial treatment at all times adhered to intensified treatment or national guidelines that targets co-existing risk factors for later diabetes-related complications. About eighty patients were assigned to each group with implementation of both pharmacological and behavioural treatment followed by structural approach. Six study visits were completed at Steno Diabetes Centre at an average of 1.9, 3.8, 7.8 and 13.3 years, terminated after 21.2 years. Out of 160 patients, 120 patients completed the interventional study with follow-up investigations initiated for investigating differences in median time. Three endpoints were considered for the study. Between the two treatment groups, the difference was studied after randomization with or without CVD. Secondary endpoint was cardiovascular events rate, mortality, and diabetic neuropathy events as tertiary endpoints.

Methodology

Intention-to-treat principle was used for statistical analysis for both groups of patients. The randomized control trial (RCT) method was advantageous for the study as it aided in comparing the intensive therapy directly to conventional therapy for establishing superiority. This methodology is helpful in making causal differences and gives strongest empirical evidence for study efficacy of a treatment (McCusker and Gunaydin 2015). It greatly minimized selection bias and considered a gold standard method. In this study, the author allocated European descent, Danish patients with microalbuminuria and type 2 DM randomly in receiving intensive, multi-factorial intervention as compared to conventional diabetic treatment. It also helped to seek in measuring and comparing the intervention outcome after the patients received the treatment. However, RCT has certain limitations. The long trial running time may have resulted in loss of relevance and block randomization used may have resulted in selection bias (Nardi 2018).

Results: 42 and 24 patients in original intensive and original conventional-therapy group respectively completed the entire period of follow-up and median observation time was calculated to be 21.2 years after follow-up completion ranging from 20.2-21.9 years. After the follow-up, the observed mean time for first CVD event or death in conventional-therapy was 8 years as compared to 16.1 years among patients in intensive-therapy group (95% CI 4.0, 12.6 years). After overall adjustment, mortality rate was reduced by 45% and 21% absolute risk reduction in intensive-therapy group during the entire follow-up period. Moreover, the results also depicted that death reported from cardiovascular causes reduced by 62% among patients who received original intensive-therapy. Cardiovascular events were also studied and it was found that about 35 patients experienced CV event as compared to 51 patients who were in conventional therapy group. This result corresponds to the fact that there was RR reduction by 51% and absolute risk reduction rate by 20% between the two groups. This result illustrated that there was reduced mortality due to reduction in CVD risk (Gæde et al. 2016).

Microvascular complications and its progression were also studied by sensitivity analysis and it was found that retinopathy progression decreased by 33% among patients in intensive-therapy group. There was reduction in blindness in one eye with 95% CI 0.23, 0.98, p =0.044 or HR of 0.47. Macroalbuminuria and autonomic neuropathy also reduced by 48% and 41% respectively in intensive-therapy group.

The results also depicted that there was reduction in mortality rates as there was decreased CVD incidence rates and related mortality among patients in the original intensive-therapy group. For all endpoints, RR reductions and absolute risk were in line that corresponded with previous findings confirming the fact that original intensive-therapy for type 2 DM and microalbuminuria was durable, multi-factorial, and intensified. Moreover, in the Steno-2 study, although, there were high progression rates for microvascular complications, yet there was significant and relevant risk reduction for neuropathy, retinopathy and nephropathy, blindness with reduction in risk for renal disease at end stage. The author accepted the initial hypothesis that CVD events and related risk could be reduced with intensive-therapy in patients with type 2 DM and microalbuminuria as compared to single-risk-factor interventions trials that were performed earlier (Gæde et al. 2016).

Results

Conclusions/Recommendations: From the results, the author concluded that multi-factorial, intensified treatment of type 2 DM with microalbuminuria was found to be 7.8 years as compared to patients who received conventional treatment. There was increase in length of median life by 7.9 years, 21.2 years of entire follow-up and there was increase in matching of gained years and free from cardiovascular complications in patients with microalbuminuria and type 2 DM. Moreover, this approach of original intensive-therapy was of great significance in controlling risk factors and complications of type 2 DM. This therapy was broadly implemented as per clinical guidelines and the findings led to more focus on the preventative effects of the disease (Nathan 2015).

The early intervention concept in patients at low risk has proven to be quite beneficial for the combined blood pressure and lipid treatment at intermediate risk, without the CVD risk. The Steno-2 study in the study is robust as the endpoints data were considered complete as the relevant data were of high quality. Moreover, the concomitant treating of multiple risk factors was found to be of profound importance that was supported by previous findings in the paper. The study design that was employed for the study resembled real life situation and researchers had no direct influences on lifestyle or medicine compliance of the participants.

In trials that involves beneficial and long-term effects are termed as “legacy effect” or “metabolic memory” and in such studies, at the end of trial, protocol was stopped and subsequent risk factor control was not reported or relaxed. However, in this Steno-2 study, the patients continued with the original intensive-therapy and treatment goals and patients in group of conventional therapy started with the same treatment goals of intensified therapy during the follow-up period. The study also interpreted that continuous benefits that was witnessed in the trial was a direct consequence of intensification during the early intervention in low absolute risk patients for diabetic complications. This is compared to a situation where increase in vascular damage is already established with intensification in later stages of disorder (Gæde et al. 2016).

Cardiac nursing care: Within the clinical context, original intensive therapy is significant to cardiac nursing care as it is beneficial in reducing the risk of neurologic and microvascular complications of type 1 DM and microalbuminuria. This therapy is significant as compared to conventional therapy for reducing the risk of long-term incidence of CVD events associated with type 2 DM. This therapy can be helpful for cardiac nurses to reduce conditions of CVD that are associated with long-term complications in type 2 DM through CVD risk management education. The cardiac nurse can play a vital role in better management of type 2 DM cardiac complications and in reducing the risk of CVD events in patients through original intensified therapy (Gæde et al. 2016).

Future studies: Until recently, there are side effects that are reported in long-term use of intensive therapy in patients with type 2 DM. There is also prevalence of severe hypoglycaemic conditions in patients with targeted treatment for HbA_1c (García-Pérez et al. 2013)_. There is need for future studies to study the side effects of long-term use of this therapy to decrease mortality and severe CVD events. Still, patients with type 2 DM undergoing intensive therapy have increased risk for mortality.  Therefore, there is a need for further studies to understand the efficacy of this therapy in reducing cardiac related complications in patients associated with type 2 DM

References

Gæde, P., Oellgaard, J., Carstensen, B., Rossing, P., Lund-Andersen, H., Parving, H.H. and Pedersen, O., 2016. Years of life gained by multifactorial intervention in patients with type 2 diabetes mellitus and microalbuminuria: 21 years follow-up on the Steno-2 randomised trial. Diabetologia, 59(11), pp.2298-2307.

García-Pérez, L.E., Álvarez, M., Dilla, T., Gil-Guillén, V. and Orozco-Beltrán, D., 2013. Adherence to therapies in patients with type 2 diabetes. Diabetes Therapy, 4(2), pp.175-194.

Harrison, L.B., Adams-Huet, B., Li, X., Raskin, P. and Lingvay, I., 2014. Intensive therapy in newly diagnosed type 2 diabetes: results of a 6-year randomized trial. Journal of Investigative Medicine, 62(4), pp.676-686.

Inzucchi, S.E., Bergenstal, R.M., Buse, J.B., Diamant, M., Ferrannini, E., Nauck, M., Peters, A.L., Tsapas, A., Wender, R. and Matthews, D.R., 2015. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes care, 38(1), pp.140-149.

Look AHEAD Research Group, 2013. Cardiovascular effects of intensive lifestyle intervention in type 2 diabetes. New England journal of medicine, 369(2), pp.145-154.

McCusker, K. and Gunaydin, S., 2015. Research using qualitative, quantitative or mixed methods and choice based on the research. Perfusion, 30(7), pp.537-542.

Nardi, P.M., 2018. Doing survey research: A guide to quantitative methods. Routledge.

Nathan, D.M., 2015. Diabetes: advances in diagnosis and treatment. Jama, 314(10), pp.1052-1062