Management of Postprandial Blood Glucose in Diabetes Mellitus

Patients with type-2 diabetes have more than half the day in the post meal state. Elevation in post meal plasma glucose is due to loss of first phase insulin secretion, decreased insulin sensitivity in peripheral tissues and consequent decreased suppression of hepatic glucose output after meals due to insulin deficiency. Elevated or exaggerated post meal response is directly responsible for endothelial dysfunction and pro-atherogenic states. Post-meal hyperglycemia is a prominent early defect in type-2 diabetes patients.


Introduction
80% of total caloric intake is carbohydrate rich in our country. The higher glucose load in the diets is responsible for an exaggerated prandial glycemic response. This in turn leads to a higher lipaemic peak which has a direct correlation with cardiovascular disease. Even before diagnosis of clinical diabetes, these metabolic abnormalities are first evident as elevation in postmeal plasma glucose. HbA1c levels reflect overall glycemic exposure and are determined by both fasting and PPG exposure. In a study patient who achieved fasting plasma glucose levels of < 100 mg/ dl, 64% achieved HbA1c level of <7% and of patients who achieved PPG levels < 140 mg/dl, 94% achieved an HbA1c < 7%. In diabetic patients with HbA1c levels between 6.8 to 8.9, PPG contributed to almost 70% of the HbA1c level.

Eff ect of Post Prandial Blood Glucose
Post prandial blood glucose has been linked to diabetic complications like cardiovascular problems. Achieving diet control in diabetic patients remains a significant challenge in our country.
The value of good glycemic control by intensified insulin therapy in type 1 diabetes patients has been established by DCCT trial.
Subsequent studies like UKPDS and Kumamoto confirm that the extent of benefit of tight control in type 2 patients also. In one study almost half the patients have post prandial values more than 70 mg over fasting values. 1/3 of patients had glucose excursion over 100 mg/dl. Elevated post prandial blood glucose with normal fasting blood glucose can cause complications like retinopathy. Some of the micro and macro vascular complications are seen even before the diagnosis of DM clinically. The Rancho Bernardo study [1] suggests that isolated post challenge hyperglycemia increase the risk of fatal CVD. Plasma glucose value more than 140 mg% at 2 hours after an OGTT defines postprandial hyperglycemia (PPHG).
It includes all cases of IGT. Post prandial glucose reduction is seen with metformin, alpha glucosidase inhibitors, pioglitazone and DPP-4 inhibitors.

Causes of High Postprandial Blood Glucose are
a. Unusually high intake of carbohydrate diet.
b. OHA or insulin when given at pre-lunch or pre-breakfast time is not able to bring post lunch blood sugar but is controlling fasting blood glucose. Any attempt to increase the dose of medication in such situation results in 5.00 pm hypo glycaemia (Evening Hypo glycaemia) hence is not the preferred mode of treatment.
c. In Type 2 DM meal stimulated insulin secretion seems to be lost. This occurs even before overt DM develops. Normally after IV Glucose, insulin peaks within 10 minutes and second phase peaks after 20 minutes. In DM insulin in 1 st phase is absent, and second stage secretion is blunted and delayed. Fasting hyper glycaemia occurs when a loss of approximately 75% in beta cells occur. Glucose monitoring in type2 diabetes mellitus seems to be more complex than previously thought, because fasting glucose is a rather poor index of glucose levels throughout the day. HbA1c seems to provide poor information on postprandial glucose levels and it provides no information on glucose excursions with meals.
Post-meal is one of the earliest defects in diabetes and is the predominant contributor to HbA1C at values below 8.4%

PPBG Elevations and DM
Glucose is a potent inducer of oxidative stress and induces free radical oxidation of low-density lipoprotein. This leads to increased vessel wall atherogenesis. Increased PPBG produces dyslipidemia, activates prothrombotic activity and reduces insulin sensitivity. All these factors lead to chronic complications of DM.
In gestational diabetes normalizing postprandial glucose levels are associated with a better outcome of pregnancy. [2] There is epidemiologic evidence to show that postprandial hypoglycemia correlated directly with incidence of retinopathy, nephropathy,  Helsinki Policemen Study (1985) -9 1/2-year follow-up [11] CAD events correlated with ½ hour postprandial hyperinsulinemia 10 Diabetic Early Pregnancy Study [12] High birth weight of newborn correlated well with mother's 3rd trimester postprandial elevated glucose level 11 Diabetic Intervention Study [13] Postprandial blood sugar and not FBS was independent risk factor for MI and cardiac death 12 Bedford Survey [14] Protection from CAD lost when elevated postprandial blood sugar occurred 13 Rotterdam Study [15] Increased postprandial blood sugar and intellectual functions deteriorated -impaired cognitive function 14 DECODE* [16] 2-hr. blood glucose levels following 75 gm OGTT better predictor of all cause and cardiovascular deaths than FBG 15 Chicago Heart Association [17] Increased risk of CVD mortality with higher PPG levels 16 Temelkova Kurktschiev, et al. [18] 2-hr blood glucose level and spikes more strongly associated with CIMT (carotid intima medial thickness) than FPG or HbA1c

17
Campanian post-prandial hyperglycaemia study [19] Reduction in post-meal but not FPG, associated with reduction in CIMT *DECODE-Diabetes epidemiology collaborative analysis of diagnostic criteria in Europe.

Management [20]
A drug should reduce rate of glucose entry, improve meal Lispro [22] insulin is an insulin analogue, has proline from position B28 to B29, thus Lispro hexamers dissociate more readily than regular human insulin hexamers into monomers. It is indicated for reduction of pre-prandial and post-prandial blood sugar. As it is a short acting insulin and it has to be used in conjunction with longer acting human insulin. It can-be taken with meals. It has rapid onset action and shorter duration of action than regular human insulin.

Conclusion
Persistent post prandial hyper glycaemia in a diabetic is not desirable. It will lead to long term macro-vascular and micro vascular complications. Every effort should be made to bring it down to normal acceptable level. Current modalities of therapy to bring down prandial hyper glycaemia are briefly reviewed.