| Management |
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| Post-Prandial Hyperglycemia in The Context of Diabetes Specific Complications. |
| - Dr Moutusi Raychaudhuri MD DM, Dr Sainath Mukherjee MD DM |
Dept. Of Endocrinology, IPGMER & SSKM Hospital, Kolkata
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| Type 2 DM leads to certain diabetes specific complications. These include both the microvascular & the macrovascular complications. The DCCT, UKPDS & Kumamoto studies establish the beneficial effects of lowering glycated hemoglobin in respect to the microvascular complications i.e. nephropathy, neuropathy & retinopathy. However, the beneficial effects in relation to cardiovascular disease (CVD) are less evident & this was postulated to be due to other comorbidities. Then, the Rancho Bernardo study went on to suggest that isolated post-challenge hyperglycemia increases the risk of fatal CVD. Post-prandial hyperglycemia thus emerged as a separate entity & its independent role in the accelerated atherogenesis of diabetes was focused upon. |
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| A plasma glucose value more than 140 mg% at 2 hrs. after an OGTT, defines post-prandial hyperglycemia (PPHG). It therefore includes all cases of IGT as well. |
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| The relative contribution of post-prandial glucose level to the HbA1c level remains a gray area. In contrast to the earlier belief that HbA1c levels related closely to the fasting glucose levels, some recent studies opine that there is a better correlation with post-prandial glucose levels. |
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| The questions therefore which are to be answered are |
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- Does PPHG play a unique role in accelerated atherosclerosis?
- Is specific lowering of PPHF beneficial?
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| The normal post-prandial state: |
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| Meal and post-meal period define the post-prandial state, which covers a little more than half the daytime period. Normally plasma glucose levels fluctuate within a narrow range in the post-prandial period. The glucose absorbed from intestine adds to the plasma glucose. It is accompanied by prompt sensing by the ß cell of the pancreas. Insulin levels rise, glucagons goes down, hepatic glucose output falls & peripheral tissues start utilizing & storing glucose. |
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| The post-prandial state in diabetes: |
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| Due to ß cell dysfunction there is altered insulin pulsatility both in timing & in amplitude. Physiological plasma glucose excursions fail to entrain high frequency insulin pulsatility. There is loss of first phase insulin secretion with an increase in proinsulin and split insulin levels. Low insulin & high glucagons levels increase hepatic glucose output. Insulin resistance aggravates the non-suppresibility of hepatic glucose output and also reduces peripheral glucose uptake. GLUT 2 & GLUT 4 are potential candidates in the pathogenesis of PPHG. All these added together lead to excessive post-prandial glucose excursions. |
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| Post-prandial hyperglycemia and atherosclerosis: |
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| There is increasing evidence that the post-prandial state is an important contributing factor in the development of atherosclerosis. The post-prandial state is characterized by transient plasma variations in carbohydrate, lipids, coagulation system, & endothelial function. These variations would have an impact on the metabolism of several tissues. |
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| The post-prandial state in a Type 2 DM patient is considered crucial mainly because of the tissue toxicity of glucose. Effects of glucose on the arterial wall include immediate effects and long-term effects. Among the immediate effects, high glucose interferes with the endothelial function. There is activation of protein kinase C, increased expression of adhesion molecules & uptake of leucocytes into the endothelium. |
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| The long term effects are brought about by non enzymatic glycosylation of various proteins. During the post-prandial period in a Type 2 DM patient there is diminished free fatty acid utilization. This is consistent with the metabolic abnormality of increased triglyceride and low HDL. The post-prandial state is therefore potentially atherogenic and post-prandial hyperglycemia has been shown to be a good predictor of CAD. |
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| Post-prandial, hyperinsulinemia and the associated procoagulant state perhaps further contribute to accelerated atherosclerosis. The final common pathway is probably through generation of oxidative stress. |
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| Post-Prandial Hyperglycemia & Diabetic Complications: |
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| In gestational diabetes, normalizing post-prandial glucose levels is associated with a better outcome of pregnancy than normalizing pre-prandial glucose levels. |
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| There is epidemiologic evidence to show that PPHG correlates directly with incidence of retinopathy & nephropathy. |
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| The relationship of PPHG and CVD is one of the recently focused areas in diabetes. The DECODE study shows that mealtime glucose spikes are independent risk factors for cardiovascular mortality & the measurement of fasting levels alone do not accurately identify individuals at increased risk of death. In the Whitehall study, the mortality doubled in those with post-prandial levels between 96 mg/dl & 196 mg/dl compared to those with levels < 96 Ad. In the lslington diabetes survey the prevalence of major CVD increased from 9% in those with normal glucose tolerance to 19 % in those with IGT. |
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| In conclusion, it is being increasingly realized that post-prandial hyperglycemia contributes significantly in the genesis of diabetes specific complications. A large number of prandial glucose regulators, are already in the market. Some newer drugs, which target the post-prandial values specifically, are on their way. In the meantime we are awaiting some well-designed randomized control trials to establish the benefits of lowering post-prandial glucose values. Let us hope that an all-pervasive approach to control glycemia will significantly eliminate the morbidity. |
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