Glucose “peak” and glucose “spike”: Impact on endothelial function and oxidative stress

doi:10.1016/j.diabres.2008.07.015

Diabetes Research and Clinical Practice

Volume 82, Issue 2, November 2008, Pages 262-267

https://doi.org/10.1016/j.diabres.2008.07.015 Get rights and content

Abstract

Aim

Data suggest that 2 h hyperglycaemia during an OGTT is less predictive for cardiovascular disease of the glucose “spike” (the difference between the baseline glucose level and the “peak” hyperglycaemia during the test).

Methods

A euinsulinemic hyperglycaemic clamp at 10 and 15 mmol/l glucose, with or without vitamin C, was given in increasing steps in diabetic and normal subjects. Moreover, a hyperglycaemic clamp, 10 mmol/l, was performed in two groups of diabetic patients with different levels of fasting glycaemia. In both the experiments flow mediated dilation and nitrotyrosine were measured.

Results

Glucose at 10 and 15 mmol/l resulted in a concentration-dependent induction of endothelial dysfunction and oxidative stress. Vitamin C counterbalanced this effect. The increase of glycaemia to 10 mmol/l induced a significant endothelial dysfunction and increased nitrotyrosine in both the groups of diabetics with different fasting glycaemia. However, when the delta (the difference between the basal value and the peak value) for endothelial function and nitrotyrosine was evaluated, patients with lower basal values showed a worse outcome.

Conclusions

Our data suggest that at the same level of hyperglycaemia the grading of the endothelial dysfunction is almost super imposable, but clearly worse in terms of delta from fasting glycaemia.

Section snippets

Subjects

30 type 2 diabetic patients and 10 healthy subjects were recruited. The protocol of the study was approved by the Ethics Committee of our institution. All subjects gave informed consent before being tested.

The diabetic patients had newly diagnosed (within 6 months) type 2 diabetes mellitus and were on diet alone and had no evidence of any cardiovascular complications.

Hyperglycaemic euinsulinemic clamp

The hyperglycaemic euinsulinemic clamp was a modification of the method used by Del Prato et al. [20]. In order to maintain

Protocol A: stepwise glucose increase

In both normal and diabetic subjects, the increase of glycaemia from basal levels to 10 mmol/l for 3 h and then from 10 to 15 mmol/l for 3 h produced a stepwise significant increase in endothelial dysfunction and nitrotyrosine levels (Fig. 1, Fig. 2). Vitamin C administration completely prevented the effects of acute hyperglycaemia at both 10 and 15 mmol/l (Fig. 1, Fig. 2).

Protocol B: single glucose “spike”

Two groups of patients were divided based upon their basal plasma glucose levels. Basal endothelial function was lower, and

Discussion

In this study we were able to confirm that an acute increase of glycaemia induces an endothelial dysfunction. However, we have also shown, for the first time, that this effect is glucose concentration dependent, and that in diabetic patients this does not depend upon the basal level of glycaemia already present. Finally, we have clear proof that oxidative stress plays a key role in these phenomena.

Many reports have already shown that an acute increase of glycaemia induces endothelial

Conflict of interest

The authors do not have conflicts of interest.

References (35)

H. Kawano et al.
Hyperglycemia rapidly suppresses flow-mediated endothelium-dependent vasodilation of brachial artery
J. Am. Coll. Cardiol.
(1999)
C.J. Rodriguez et al.
Relation of plasma glucose and endothelial function in a population-based multiethnic sample of subjects without diabetes mellitus
Am. J. Cardiol.
(2005)
A.B. Goldfine et al.
Family history of diabetes is a major determinant of endothelial function
J. Am. Coll. Cardiol.
(2006)
The Diabetes Control and Complications Trial Research Group
The effect of intensive treatment of diabetes on the development and progression of longer complications in insulin-dependent diabetes mellitus
N. Engl. J. Med.
(1993)
UK Prospective Diabetes Study (UKPDS) Group
Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes
Lancet
(1998)
C. Stettler et al.
Glycemic control and macrovascular disease in types 1 and 2 diabetes mellitus: meta-analysis of randomized trials
Am. Heart J.
(2006)
I.M. Stratton et al.
Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study
BMJ
(2000)
K.T. Khaw et al.
Glycated haemoglobin, diabetes, and mortality in men in Norfolk cohort of european prospective investigation of cancer and nutrition (EPIC-Norfolk)
BMJ
(2001)
H.C. Gerstein
The relationship between dysglycaemia and cardiovascular and renal risk in diabetic and non-diabetic participants in the HOPE study: a prospective epidemiological analysis
Diabetologia
(2005)
P.B. Mellen et al.
Post-challenge glucose predicts coronary atherosclerotic progression in non-diabetic, post-menopausal women
Diabet. Med.
(2007)

The DECODE Study Group

Glucose tolerance and mortality: comparison of WHO and American Diabetes Association diagnostic criteria

Lancet

(1999)

B. Balkau et al.

High blood glucose concentration is a risk factor for mortality in middle-aged nondiabetic men: 20-year follow-up in the Whitehall Study, the Paris Prospective Study, and the Helsinki Policemen Study

Diabetes Care

(1998)

M. Coutinho et al.

The relationship between glucose and incident cardiovascular events: a metaregression analysis of published data from 20 studies of 95,783 individuals followed for 12.4 years

Diabetes Care

(1999)

A. Ceriello

Postprandial hyperglycemia and diabetes complications: is it time to treat?

Diabetes

(2005)

T.S. Temelkova-Kurktschiev et al.

Postchallenge plasma glucose and glycemic spikes are more strongly associated with atherosclerosis than fasting glucose or HbA1c level

Diabetes Care

(2000)

K. Esposito et al.

Postmeal glucose peaks at home associate with carotid intima–media thickness in type 2 diabetes

J. Clin. Endocrinol. Metab.

(2008)

R.J. Esper et al.

Endothelial dysfunction: a comprehensive appraisal

Cardiovasc. Diabetol.

(2006)

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View full text

Glucose “peak” and glucose “spike”: Impact on endothelial function and oxidative stress

Abstract

Aim

Methods

Results

Conclusions

Section snippets

Subjects

Hyperglycaemic euinsulinemic clamp

Protocol A: stepwise glucose increase

Protocol B: single glucose “spike”

Discussion

Conflict of interest

J. Am. Coll. Cardiol.

Am. J. Cardiol.

J. Am. Coll. Cardiol.

The effect of intensive treatment of diabetes on the development and progression of longer complications in insulin-dependent diabetes mellitus

N. Engl. J. Med.

Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes

Lancet

Glycemic control and macrovascular disease in types 1 and 2 diabetes mellitus: meta-analysis of randomized trials

Am. Heart J.

Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study

BMJ

Glycated haemoglobin, diabetes, and mortality in men in Norfolk cohort of european prospective investigation of cancer and nutrition (EPIC-Norfolk)

BMJ

The relationship between dysglycaemia and cardiovascular and renal risk in diabetic and non-diabetic participants in the HOPE study: a prospective epidemiological analysis

Diabetologia

Post-challenge glucose predicts coronary atherosclerotic progression in non-diabetic, post-menopausal women

Diabet. Med.

Glucose tolerance and mortality: comparison of WHO and American Diabetes Association diagnostic criteria

Lancet

High blood glucose concentration is a risk factor for mortality in middle-aged nondiabetic men: 20-year follow-up in the Whitehall Study, the Paris Prospective Study, and the Helsinki Policemen Study

Diabetes Care

The relationship between glucose and incident cardiovascular events: a metaregression analysis of published data from 20 studies of 95,783 individuals followed for 12.4 years

Diabetes Care

Postprandial hyperglycemia and diabetes complications: is it time to treat?

Diabetes

Postchallenge plasma glucose and glycemic spikes are more strongly associated with atherosclerosis than fasting glucose or HbA1c level

Diabetes Care

Postmeal glucose peaks at home associate with carotid intima–media thickness in type 2 diabetes

J. Clin. Endocrinol. Metab.

Endothelial dysfunction: a comprehensive appraisal

Cardiovasc. Diabetol.