Acarbose And Glycemic Pentad Diabetes is lifestyle-oriented

Diabetes and Acarbose A Glycemic Pentad

Diabetes and glycemic disturbances are lifestyle-oriented metabolic diseases characterized by a decrease in insulin sensitivity. Under such circumstances, accurate monitoring of the patient’s condition is the root of choosing an appropriate treatment. Glycaemic pentad grants a multidimensional approach to treating diabetes. It proposes that the therapy should target the clinical aspects and contemplate the socio-economic and psychological conditions of the patients.1 In this regard, the current article discusses the efficacy of acarbose on glycemic pentad in diabetic patients.

The American Diabetes Association (ADA) endorses aiming the peak postprandial plasma glucose levels to <180 mg/dl, glycated hemoglobin (HbA1c) levels to <7.0%, and pre-prandial glucose levels to 80–130 mg/dl (glycemic triad) to attain a better glycemic control.

Nevertheless, several studies have recorded that, despite focusing on the glycemic triad, diabetic patients increasingly suffered from diabetic retinopathy and other complications of diabetes.
Thus, a forum of 55 Indian diabetologists was instituted, which came to the consensus that the combination of five components – fasting plasma glucose (FPG), postprandial plasma glucose (PPG), HbA1c, glycemic variability, and quality of life (QoL) called as a glycemic pentad, should be considered milestones for any therapy in the management of diabetes.1 Glycemic pentad surpasses the confinements of the triad. It thus assists in determining the most suitable therapy for the patient, which plays a crucial role in managing diabetes and associated comorbidities. This further leads to improvements in patient outcomes.1 Acarbose and Diabetes Management Acarbose has been used for more than twenty years to manage hyperglycemia. The properties of acarbose are quite different from other anti-diabetic medications as it has an exclusive mode of action in the gastrointestinal tract. Patients on long-standing therapy to manage hyperglycemia are not only interested in the efficiency of treatment but are also concerned with the safety and adverse effects of their medications. To such patients, acarbose is an expedient treatment option for managing their condition.2 According to a non-interventional observational study, acarbose is effective and safe in Indian T2DM patients. Furthermore, acarbose helps in reducing weight and has excellent patient compliance. This study involved a total of 1996 Indian patients (mean age: 50.1 years standard deviation (SD) 10.7; mean BMI: 27.2 kg/m2 SD: 4.4). Most of these patients, at preliminary visit, were prescribed acarbose 50 mg/day (n = 1094/1996; 54.8%), 100 mg/day (n = 504/1996; 25.3%), 25 mg/day (n = 228/1996; 11.4%), or 150 mg/day (n = 133/1996; 6.7%). However, by the final visit, the number of patients receiving acarbose 50 mg/day reduced to 33.7% (672 patients), whereas patients receiving 100 mg/day and 150 mg/day of acarbose had augmented to 43.8% (874 patients) and 14.0% (280 patients), respectively. Furthermore, after 12.4 weeks, it was observed that the mean 2-hour PPG value significantly lowered from 243.9 mg/dl to 169.5 mg/dl, whereas fasting blood glucose (FBG) reduced substantially from 158.3 mg/dl to 120.4 mg/dl. In the last follow-up, the FBG, PPG, and HbA1c were observed to be declined among 90.6%, 94.4%, and 52.4% of patients. Additionally, the mean reduction in waist circumference was observed to be 1.6 cm, and the mean reduction in weight was found out to be 1.4 kg. Also, compliance with acarbose was reported in 97.09% of patients, and no serious adverse events were reported.4 Effect of Acarbose on Glycemic Pentad Effect of Acarbose on HbA1c: The efficacy of acarbose as monotherapy and combination therapy has been confirmed in numerous studies worldwide.5 According to the observations from a network meta-analysis performed to evaluate the effectiveness and safety of add-on antidiabetic therapies in metformin uncontrolled T2DM patients; acarbose was estimated to change the HbA1c value by -0.79 (-1.09, -0.48).6 Effect of Acarbose on Glycemic Variability: Glycaemic variability is a significant parameter to be considered in diabetes management to achieve optimal glycemic control. Several clinical trials have concluded that acarbose therapy effectively controls glycemic variability, thereby improving macro and microvascular consequences in T2DM patients.7,8 According to an open-labeled, randomized study, acarbose combined with metformin efficiently reduced interday and intraday glucose variability. The study involved a total of 40 T2DM patients (age between 30–70 years). All patients were treated with metformin therapy (500 mg thrice daily) for 8 weeks and were later randomized equally to receive 100 mg of acarbose or 5 mg of glibenclamide three times daily for the subsequent 16 weeks. The results concluded that measures of glycemic variability such as SD, mean of daily differences, continuous overall net glycemic action, and mean amplitude of glycemic excursions were substantially reduced when treated with acarbose compared to glibenclamide. Compared with metformin monotherapy, the addition of acarbose provided additional benefits of weight reduction and shorter durations of hyperglycemia.7 Effect of Acarbose on FPG and PPG: In terms of measuring glycemic efficacy, the table below summarizes clinical studies that display the efficacy of acarbose on FPG and PPG of diabetic patients. Effect of Acarbose on Quality of Life: According to a study, supplementing acarbose to the existing treatment of diabetic patients led to improvements in life expectancy and quality-adjusted life expectancy. Furthermore, the addition of acarbose to the therapy was also observed to provide excellent value for money over patient lifetimes, thereby improving the patients’ quality of life. The study utilized a validated computer simulation called ‘the CORE diabetes model’ to distend long-term clinical outcomes in T2DM patients receiving acarbose or placebo along with the existing treatments.

The simulation was run over a period of 35 years to apprehend the progression of all pertinent complications in patient lifetimes (baseline age: 61 ears; baseline duration of diabetes: 7 years; mean HbA1c: 8.50).13 It was observed that acarbose treatment was connected with advancements in discounted life expectancy (0.21 years) and quality-adjusted life expectancy (0.19 of quality-adjusted life-year).13 Furthermore, the extensive sensitivity analyses concluded that the results obtained were robust under discrepancies in a range of assumptions.

Overall, it can be stated that acarbose can be effectively utilized in managing diabetes and could potentially represent a better option for glycemic control. Acarbose effectively reduces HbA1c, PPG, and FPG, manages glycemic variability, and improves the QoL of diabetic patients, thereby displaying the positive effect of every element of the glycemic pentad. The previous video discusses 360° Control In Newly Diagnosed Type 2 Diabetes Patients. Click here to know more.

GV IS AS IMPORTANT AS HbA1c

The type 1 diabetes patients in DCCT intensively treated group had lesser microvascular complications than conventionally treated group. HbA1c variability was proposed to explain the development of retinopathy and nephropathy in conventional group.[6] The positive association with cardiovascular risk factors, supports the possibility of relationship between glucose variability and cardiovascular morbidity and mortality.

Most studies have shown strongest correlations between A1c and mean plasma glucose levels and it is recognized as reliable marker in glycemic stability and its direct consequence, an excess rate of glycation.[18,19,20] However, there are other mechanisms in the development of diabetic complications and the fact that it is the exposure of glucose, which is measured by standard A1c, and does not include the peaks and nadirs.

The new formula devised by David M Nathan, takes into consideration of multiple self monitored blood glucose values and is depicted as ‘A1c Derived Average Glucose’ (ADAG): eAG (mg/dl) = 28.7 × A1C-46.7.[21,22] The average derived value which includes GV might explain in diabetic complication of hypoglycemia with near normal HbA1c in the DCCT group.

GV AND DAY TO DAY CONTROL

The Staub-Traugott effect,[23] improvement of carbohydrated tolerance following repeated glucose administration was proposed as early as 1921. This effect has been demonstrated after oral and intravenous administration of glucose. Sandra Bonuccelli et al. in their study using two sequential, equal oral glucose loads over a 6-h time period concluded that, higher glycemic excursions in response to the first load was associated with a higher potentiation factor during the second load, suggesting that the priming effect of hyperglycemia was the basis for the subsequent potentiation of insulin secretion. Glucose potentiation and stronger suppression of endogenous glucose release are the main mechanisms underlying the Staub-Traugott effect. Improved tolerance to sequential glucose loading is an important determinant of day-to-day glycemic exposure, suggesting how glycemic exposures are minimized in our body.

GV AS THERAPEUTIC END POINT

The target GV has been a topic of debate, it was proposed by Monnier et al.,[19] that 40 mg/dl as the target level of glucose variability and more so glucose variability was found to be independent predictor of chronic diabetic complications besides HbA1c. In nondiabetic critically ill patients diminishing hyperglycemic excursions will improve mortality. Also as in recent studies like action to control cardiovascular risk in diabetes (ACCORD) study, it is to be noted that hypoglycemia need to be avoided.

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Dr. Rajesh Jain

Dr. Rajesh Jain MD PG Diploma Diabetes, UK

The diabetesasia is the advocate for the people currently living with diabetes Burden & NCDs Risk. Global Diabetes Walk campaign remind us to Prevent diabetes.

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