Management of Post Prandial Hyperglycemia: An Indian Consensus statement on AGIs

Raj P. Br J Med Health Res. 2016;3(5):1-22.

Background

Large controlled clinical trials have demonstrated that intensive treatment of diabetes can significantly decrease the development and/or progression of microvascular and macrovascular complications of diabetes. Postprandial hyperglycemia (PPHG) is a very frequent phenomenon in people with type 1 and type 2 diabetes and can occur even when overall metabolic control appears to be adequate as assessed by HbA1c levels. This is supported by findings from a study conducted on 3,284 people with non-insulin treated T2DM demonstrated that a post prandial blood glucose value of more than 8.9 mmol/l (160 mg/dL) was recorded at least once among 84% of the patients, even among those with good glycemic control. Until recently, the predominant focus of diabetes therapy has been on lowering HbA1c levels, with a strong emphasis on fasting plasma glucose. Although control of fasting hyperglycemia is necessary, it is usually insufficient to obtain optimal glycemic control.

Focus on PPHG

PPHG is strongly associated with the carbohydrate content of the diet which is one of the major sources of food in Indian diet. Most studies confirm that the amount and type of carbohydrate consumed in a meal is a major determinant of the PPHG excursion. Consumption of carbohydrate-rich foods lead to alteration in blood glucose levels or glycemic index (GI). Consumption of rice is very high in South India which is associated with 4-5-fold increase in risk of diabetes. Furthermore, a recent dietary survey from India estimated that dietary carbohydrates account up to 64% of daily calories in patients with T2DM. Also, PPHG leads to higher lipemic peaks and links to CVD in patients with T2DM. Thus it may be anticipated that Asians tend to show higher rates of PPHG, increased activity of glucosidase enzyme and incretin hormones in the gut. Therefore, there is a growing need to employ intense measures for reducing PPHG excursions and excessive glycemic readings. Summary of postprandial hyperglycemia guidelines are given below in the table.

Table: Summary of post prandial hyperglycemia guidelines

Role of Indian dietary and lifestyle habits on PPHG

• As the Indian diet is rich in carbohydrate, the incidence of PPHG is reported to be greater in the Indian population than the Western world
• Traditional Indian diets are carbohydrate-rich; sometimes, as high as 80% of the macronutrient composition
• Wheat is largely consumed in Maharashtra and Northern India, while rice and its products predominates the South Indian meal. Furthermore, Indians have sweet tooth resulting in glycemic spikes
• The higher glucose load in the Indian diet leads to greater prandial glycemic excursion, increased glucosidase and incretin in activity in the gut which leads to higher lipemic peaks and associated cardiovascular disease
• Additionally, consuming large portions and more frequent meals is a common habit observed in Indians thus contributing to higher PPHG levels
• Lack of exercise is also considered one of the major reasons behind the increased prevalence of diabetes in Indians

Role of alpha-glucosidase inhibitor in managing PPHG

α-Glucosidase inhibitors (AGIs) control diabetes by inhibiting  glucosidase enzymes that limits the breakdown from starch and disaccharides, the major carbohydrate component in food. Through competitive inhibition of this enzyme, AGIs delay intestinal carbohydrate absorption and attenuate PPHG excursions. Voglibose, Acarbose and Miglitol are commercially available AGIs for treatment of patients with T2DM. Some of the key benefits of Voglibose includes:

• By controlling PPHG, Voglibose causes about 34% risk reduction in development of new cases of hypertension and about 49% risk reduction in cardiovascular diseases
• The inhibitory activity of Voglibose on maltose and sucrose is reported to be 190- 270 times higher than that of Acarbose and about 100 times higher than that of Miglitol
• Voglibose also has a better safety profile with only ~7% adverse drug reactions compared to Acarbose (~33%), and Miglitol (~17%) in T2DM patients
• Voglibose is found to reduce the progression of average and maximum carotid intima media thickness (CIMT) to -0.024 and -0.021 mm/year, respectively for 3 years in patients with T2DM treated with Sulfonylueras or Insulin
• Overall, Voglibose is an effective, safe and well tolerated treatment for diabetes, which provides cardiovascular benefits to patients with T2DM
• When adequate glycemic control i.e. PPHG level is not achieved by monotherapy with oral hypoglycemic agents (OHAs), Voglibose can be used in combination with Sulfonylurea or Metformin

Concerns with the use of Voglibose in managing PPHG

• The only concern with the use of Voglibose is gastrointestinal suffering such as bloating, flatulence, steatorrhea, and diarrhea which can be avoided by starting with a low dose and gradually elevating it

Dietary recommendations

• High fiber and low-carbohydrate diet comprising largely of fruits, vegetables, and proteins should be included in day to day living. Patients should try to decrease carbohydrate intake to 40-50%
• Consumption of refined carbohydrates should be avoided
• Brown rice should be preferred over polished white rice
• Four to five small meals containing food that are low in their GI are recommended compared to two moderately heavy meals

Lifestyle recommendations

• Patients should be advised to walk for few minutes (15-30minutes) after every meal, and must be coaxed into indulging in muscle-strengthening exercises on a regular basis
• Lastly, measures should be taken to improve awareness, regarding CVD risk with PPHG, among other practicing clinicians who treat diabetes patients as well as in diabetic patients

Thus, it was concluded that PPHG is an independent risk factor of cardiovascular complications in diabetes patients and a better predictor of glycemic control than the FPG. Considering high carbohydrate content in the Indian diet, AGIs are effective in treating Indian diabetic patients especially Voglibose as it is effective in controlling PPHG in Indian population when administered as monotherapy or in combination with other drugs.

HbA1c: Hemoglobin A1c, T2DM: Type 2 Diabetes Mellitus, CVD: Cardiovascular disease, ADA: American Diabetes Association, IDF: International Diabetes Federation, AACE: American Association of Clinical Endocrinologists, EASD: Eurapoean Association for the Study of Diabetes, FPG: Fasting plasma glucose