Type 2 diabetes mellitus is characterised by progressive and inexorable decline in beta cell function so much so that at onset almost 50 to 60% of beta cell function is lost, whereas, insulin resistance the other cardinal defect, gats stabilized after initial rise and remains fairly constant in the lifetime of an individual. This rapid decline in insulin secretion is unfortunately unavoidable and leads to progressive post-prandial hyperglycaemia. Targeting fasting plasma glucose is often insufficient to produce optimal HbA1c control though it is an integral part of glycemic control.
Glycemic control of an individual is best assessed by what is known as the “glucose triad” comprising of fasting plasma glucose (FPG), post prandial plasma glucose (PPPG) and glycosylated hemoglobin (HbA1c) and all three parameters of this triad need to be targeted. Traditional approach of targeting FPG (“Fix Fasting First”) is often an suboptimal strategy to achieve optimal glycemic control. Today, there is a growing understanding of the relevance of targeting post-prandial/ random plasma glucose in optimising HbA1c that is vital for prevention of both micro- and macrovasular complications of diabetes as a person spends more time in post prandial and postabsorptive than in a fasting state on any given day.
Post- prandial hyperglycemia (PPHG) is defined as net rise of glucose from premeal lowest to post meal highest point. Various bodies categorize it at different values: ADA (180 mg/dl), AACE (140 mg/dl), IDF (145 mg/dl), however, most widely accepted value is any post- prandial value more than or equal to 140 mg/dl. It can be assessed by various parameters including self-monitoring of blood glucose (SMBG), continuous glucose monitoring (CGM), HbA1c that assesses control of previous 3 months and 1,5 – anhydro-glucitol that assesses control of preceding 2 weeks. Of these, HbA1c is most widely used strategy to find out status of glycemic control. It is well known that FPG is main determinant of HbA1c at higher and PPPG at lower values, so much so that, at a value > 10.2% FPG is contributes to 70% HbA1c while at a value <7.3% main determinant of HbA1c with PPPG accounting for 70% of it. These figures are derived from Western studies. In Indians and Asians, while PPPG forms higher component of HbA1C, it still remains bigger contributor to HbA1c at its higher values (about 50% at HbA1c>10.2%). It is a common experience that it is more difficult to control HbA1c when it is closer to 7% than when it is at a higher level. In these cases, it is therefore imperative to target PPG for better control.
Fasting plasma glucose on the other hand depends on a variety of factors including:
Hence, in order to achieve HbA1c target an action is required both on FPG and PPG.
Factors responsible for PPHG are:
Hyperglycemia activates multiple mechanisms that mediate vascular damage. These include increased oxidative stress, overproduction of advanced glycosylation end products, increased activation of polyol pathway that lead to various micro- and macrovascular complications associated with PPHG.
Post prandial hyperglycemia is associated with multiple harmful effects that can be characterized on short term and long term basis:
A meta-analysis of 38 prospective studies that included 194,658 patients over a mean follow-up period of 12.0 years showed that while postmeal hyperglycaemia is linearly related to CV risk across a wide range of postmeal glucose values, the trends observed for FPG are vastly different. The study by Levitan and colleagues analysed data from a subset of the original 38 studies (12 studies that reported FPG levels and 6 studies that reported postchallenge glucose) to allow for dose-response curve estimates. Risk of CV events increased in a linear fashion without a threshold for 2-hour PPG, whereas FPG showed a possible threshold effect at 5.6 mmol/L (100 mg/dL) with a steep rise in CV disease risk above this threshold value. That mealtime glucose spikes are associated with increased risk of cardiovascular disease and mortality is well established by many landmark trials including DECODE, Pacific and Indian Ocean study, Funagata Diabetes Study and The Rancho – Bernardo Study among others.
The prevalence of T2DM is increasing exponentially throughout the country though more in urban as compared to rural areas. Prevalence of T2 DM has increased from 8% (1980) to 16% (2006) in urban India in a very short span of time, specifically in Chennai.
Changes in our lifestyle namely poor dietary habits and sedentary lifestyle is largely to blame. Cereals are staple diet in India. Carbohydrates form bulk of the total calorie intake. Since 1980, the percentage of carbohydrate intake in Indian diets has remained relatively constant and is much higher than 55-65% of total calories as recommended by WHO. Excessive intake of white rice is frequently touted to be an important factor in causation of T2DM in Indians, specially in the southern part. Dietary rice is a major contributor to glycemic load. White rice loses its protective factors during polishing that include dietary fibres, magnesium, vitamins, lignans and phytoestrogens. But, is dietary white rice the real culprit? Arguments opposing this hypothesis include
Dietary advice to prevent PPHG
Ensuing from above discussion it is clear that whereas controlling FPG has remained the bottom line of treatment in the management of T2DM, PPHG also assumes equal importance so far as to effective control of HbA1c in Indians.
Agents predominantly effective in controlling FPG:
Agents predominantly effective in controlling PPHG:
Among the insulins intermediate/ long acting basal insulins including analogues target the FPG while short/ rapid acting insulins target the PPHG. Premix insulins are a mixture of both short and long acting insulins and can potentially target both FPG and PPG. Indeed, various short term studies have confirmed this and various professional bodies such ADA, EASD, IDF and NICE support the use of premix insulins. In India, Indian Premix Guidelines also advocate the use of premix insulins as they are simple to start, convenient, no mixing required (less dosing error) and is easy to intensify using the same insulin. High ratio premix insulins can be given in cases of failure of low ratio premixes in order to intensify as it has been found to be as effective as basal bolus therapy in small studies.