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Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2007-2000
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The Journal of Clinical Endocrinology & Metabolism Vol. 93, No. 4 1345-1350
Copyright © 2008 by The Endocrine Society

Post-Meal Glucose Peaks at Home Associate with Carotid Intima-Media Thickness in Type 2 Diabetes

Katherine Esposito, Miryam Ciotola, Diego Carleo, Bruno Schisano, Luigi Sardelli, Domenico Di Tommaso, Lucio Misso, Franco Saccomanno, Antonio Ceriello and Dario Giugliano

Chair and Division of Metabolic Diseases (K.E., M.C., D.C., B.S., L.S., D.D.T., L.M., F.S., D.G.), Second University of Naples, 80138 Naples, Italy; and Warwick Medical School (A.C.), University of Warwick, Coventry CV4 7AL, United Kingdom

Address all correspondence and requests for reprints to: Dario Giugliano, M.D., Ph.D., Division of Metabolic Diseases, Department of Geriatrics and Metabolic Diseases, Second University of Naples, Piazza L. Miraglia, 80138 Napoli, Italy. E-mail: dario.giugliano{at}unina2.it.


   Abstract
Top
 Abstract
Introduction
 Patients and Methods
 Results
 Discussion
 References
 
Context: Two-hour postprandial hyperglycemia is related to chronic complications of diabetes and is currently used in the international guidelines to drive the therapy.

Objective: Our objective was to assess the size and timing of post-meal glucose peaks in the everyday life of type 2 diabetic patients and the relationship with carotid atherosclerosis.

Design, Setting, and Patients: This was an observational study performed in 644 outpatients with type 2 diabetes attending diabetes clinics located in the area of the Campania County, South Italy, who provided complete home blood glucose profiles and centralized carotid intima-media thickness (CIMT) assessment. The study was conducted from 2001–2005.

Main Outcome Measures: Incremental glucose peak (IGP) was the maximal incremental increase in blood glucose obtained at any point after the meal. CIMT was assessed by carotid sonography.

Results: The level of glycosylated hemoglobin and CIMT progressively increased across quintiles of IGP (P for trend = 0.01 for both). In univariate analysis, all examined glycemic parameters were significantly correlated with CIMT. IGP (r = 0.40; P = 0.006) showed the strongest correlation with CIMT, which remained significant in multiple linear regression analysis (R2 = 0.26; P = 0.01). IGP was associated with a significant increase of CIMT in tertiles of glycosylated hemoglobin. IGP occurred within 1 h from the start of the meal in 95% of the entire diabetic population.

Conclusion: IGPs are frequent in the everyday life of patients with type 2 diabetes, occur for most (95%) within 1 h after meal, timing of IGPs is not influenced by treatment (diet or drugs), and IGPs correlate with CIMT.


   Introduction
Top
 Abstract
 Introduction
Patients and Methods
 Results
 Discussion
 References
 
An estimated 240 million people worldwide have diabetes, which is a leading cause of death in most developed countries (1). Large prospective studies have demonstrated that intensive treatment of hyperglycemia can significantly decrease the development and/or progression of microvascular complications of diabetes (2, 3, 4, 5). Moreover, improvement in glycemic control significantly reduces the incidence of macrovascular events in both type 1 and type 2 diabetes (6). Until recently, the predominant focus of therapy has been on lowering glycosylated hemoglobin (HbA1c) levels, with a strong emphasis on fasting plasma glucose (7). However, reducing post-meal glucose excursions is equally important (8), or perhaps more important (9, 10, 11) than simply controlling fasting plasma glucose in individuals with diabetes and impaired glucose tolerance. There is also abundant evidence for a causal relationship between acute or post-meal glucose increase and microvascular/macrovascular outcomes (12, 13, 14, 15); moreover, there is no apparent glycemic threshold for reduction of complications (16, 17).

Two-hour postprandial and post-challenge hyperglycemia is a very frequent phenomenon in individuals with diabetes, can occur even when metabolic control appears to be adequate (18, 19), and is currently used to describe post-meal glycemic peaks. The 2-h time frame for measurement is recommended because it conforms to glucose guidelines published by most of the leading diabetes organizations and medical associations (20, 21). However, there is no evidence to assume that glucose peak coincides with 2-h glucose level after meal. We have attempted to give insight into the timing and size of post-meal glucose peaks occurring in the everyday life of type 2 diabetic patients, and into the respective role of glucose peak and 2-h glucose level on a consolidated surrogate marker of atherosclerosis such as carotid intima-media thickness (CIMT) (22).


   Patients and Methods
Top
 Abstract
 Introduction
 Patients and Methods
Results
 Discussion
 References
 
Patients

The rationale and preliminary observational data of the ongoing Campanian post-prandial hyperglycemia group study have been published (23). Consecutive patients with type 2 diabetes were recruited among outpatients regularly attending diabetes clinics located in the area of the Campania County, South Italy, from 2001–2005. Inclusion criteria for the initial selection of patients were: a diagnosis of type 2 diabetes for at least 6 months but less than 10 yr, age 35–70 yr, body mass index (BMI) of 24 kg/m2 or higher, HbA1c of 6.5% or higher, and treatment with diet or oral drugs. Criteria for exclusion were: need for insulin use; concomitant chronic diseases, including kidney, liver, and cardiovascular diseases; recent acute illness; or change in diet, treatment, or lifestyle within the 3 months before the initial assessment.

After the initial screening visit, with verification of inclusion and exclusion criteria, all subjects were given the same model of glucose meter (One Touch and One Touch Ultra; Lifescan, Milan, Italy) and were instructed to familiarize themselves with glucose self-assessment with such a device for a period of 1–2 wk. They were then asked to measure home blood glucose on 3 nonconsecutive days during a period of 1 month. In particular, they assessed blood glucose just before and every 30 min after the main meal of the day (whether lunch or dinner) for 2 h (five readings). They were also asked to measure fasting glucose level at least twice on 2 nonconsecutive days during the month. Patients were invited to follow their usual treatment and eat their usual diet during the month. In particular, all patients had been instructed on diet and on the glycemic index of foods by a dietician at each diabetes clinic at least 3 months before study. The diet was recommended to be followed every day of the study, including those during which patients self-assessed blood glucose. The recommended composition of the dietary regimen was the following: carbohydrates 50–60%, proteins 15–20%, total fat less than 30%, saturated fat less than 10%, and less than 300 mg cholesterol consumed per day. All patients were invited to the reference center (Department of Geriatrics and Metabolic Diseases at the Second University of Naples) for blood sampling, and assessment of CIMT.

A total of 990 patients agreed to participate in the study and provided at least one complete (five readings) home blood glucose assessment. The present report focuses on the 644 patients who provided three complete home blood glucose profiles and had had CIMT assessment. Subjects providing complete glucose profiles had similar preprandial and postprandial glucose levels, and glucose changes after meals compared with those who provided incomplete data. We focused on subjects with complete data to have all statistical analyses performed on the same sample of subjects. Informed consent was obtained from every participant (not paid volunteer), and the study was approved by the local ethics committee.

Clinical and laboratory assessment

Height and weight were measured to the nearest 0.5 cm and 100 g, respectively, with participants wearing lightweight clothing and no shoes. BMI was calculated as weight in kilograms divided by height (in meters) squared. Blood pressure was measured with a mercury manometer, on the right arm, after 5-min rest in the sitting position.

Laboratory assessment was centralized. Blood glucose and serum lipids were measured by enzymatic assays in the hospital’s chemistry laboratory, HbA1c by nephelometry, and serum insulin by RIA (Pharmacia, Milan, Italy). The interassay coefficient of variation was less than 6% for all measurements.

Carotid B-mode ultrasound

Briefly, carotid sonography was performed on a single ultrasound machine (Aloka S.p.A., Assago, Italy) with a 7.5-MHz sector scanner probe. Studies were performed in a standard fashion by a single specialist physician who was specifically trained to perform the prescribed study examination. All images were electronically stored. The measurement was made in the 1-cm segment proximal to the dilation of the carotid bulb and always in plaque-free segments. For each patient, three measurements on both sides were performed, on the anterior, lateral, and posterior projection of the far wall; the readings were then averaged. Paired CIMT measurements in the same arteries showed a high degree of reproducibility, with a mean difference in CIMT of 0.020 mm, and an intraclass correlation coefficient of 0.97 (P < 0.001).

Analysis of glucose data

All premeal and post-meal glucose values represent the average of the three home blood glucose readings. Fasting glucose is the mean of the two home blood glucose assessments. Incremental glucose peak (IGP) was defined as the maximal incremental increase in blood glucose obtained at any point after the meal. The subjects were divided into quintiles of glucose peak (IGP). The rationale was based on the fact that absolute 2-h glucose values correlate positively with both fasting and premeal glucose levels; however, absolute increase of glucose above baseline correlate negatively with premeal glucose values (19). So, IGP may represent a good indicator of the reality of glycemic spikes occurring after a meal. Other glucose parameters were fasting glucose, premeal glucose, 2-h glucose, and absolute glucose peak, which is the highest glycemic value recorded at any time after the meal. In all patients, a subanalysis of the glycemic profiles was done in patients treated with diet.

Statistical analysis

Data are presented as mean (SD) unless stated otherwise. Standard procedures were used to calculate means, SD values, and linear correlation coefficients. Log-transformed glucose concentrations over the three study periods were tested for normal distribution using the test statistic for the Kolmogorov-Smirnov Goodness of fit for continuous data. Multiple regression models were used to explore the influence of different variables on CIMT and to adjust for covariates (24). Comparisons between variables in the different groups of patients were made using one-way ANOVA, followed by Tukey post hoc testing. CIMT was assessed in tertiles of IGP and HbA1c, and the difference in CIMT in these tertiles was evaluated in trend. ANOVA for repeated measures was used to assess the reproducibility of glucose curves on different days. Changes in glucose, HbA1c, lipids over time were evaluated using either a paired t test or Wilcoxon signed-rank test, as appropriate. P < 0.05 was considered significant. All statistical analyses were performed using SPSS software (version 10.05; SPSS, Inc., Chicago, IL).


   Results
Top
 Abstract
 Introduction
 Patients and Methods
 Results
Discussion
 References
 
Study subjects providing complete glucose profiles had similar demographic and clinical features compared with subjects not providing complete glucose profiles (data not shown). The main clinical and laboratory data are included in Table 1Go. The level of HbA1c progressively increased across quintiles of IGP, as did triglycerides. Moreover, there was a progressive increase of CIMT from groups 1–5 (P for trend = 0.01 adjusted for age, lipid parameters, and HbA1c). Adjustment for age and gender only did not change the significance (P = 0.01). There was a similar trend in the relation between IGP and CIMT between sexes.


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  		TABLE 1. Clinical and laboratory data of study subjects

 
Relationships between CIMT and markers of glycemic control

When CIMT was tested for simple linear correlations against markers of glucose control, the strongest correlation was found with IGP (r = 0.40; P = 0.006). CIMT values in tertiles of IGP and HbA1c are shown in Fig. 1Go. IGPs were associated with a significant increase in trend for CIMT in tertiles of HbA1c.


Figure 1
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  		FIG. 1. CIMT (mm) in tertiles of IGP and HbA1c.

 
A statistically significant correlation was also observed with absolute glucose peak (r = 0.35; P = 0.01), 2-h glucose (r = 0.24; P = 0.02), and HbA1c (r = 0.21; P = 0.03). In contrast, CIMT did not correlate with fasting insulin (r = 0.15; P = 0.08), fasting glucose (r = 0.14; P = 0.09), total cholesterol (r = –0.02; P = 0.82), high-density lipoprotein (HDL)-cholesterol (r = –0.03; P = 0.67), and triglycerides (r = 0.14; P = 0.08). Age demonstrated a strong relation with CIMT (r = 0.38; P = 0.001).

Multiple linear regression analyses were performed to assess the independent effects of markers of diabetic control on CIMT. These markers included IGP, 2-h glucose, fasting insulin, and HbA1c. Because correlations were observed between IGP and 2-h glucose (r = 0.55; P < 0.001) in the univariate analysis, two independent models were tested, one including IGP and one including the 2-h glucose value. The adjusted R2 of model 1 (variables included HbA1c, IGP, fasting insulin) was 0.26 (P = 0.01), whereas that of model 2 (variables included HbA1c, 2-h glucose, fasting insulin) was 0.14 (P = 0.03). Apart from age, nonglycemic variables failed to enter the model when the stepwise regression analysis was applied to both glycemic and nonglycemic parameters.

Relationships among markers of glycemic control

High correlations were found between pre- and 2-h glucose levels, with r values around 0.50–0.60. Accordingly, when subjects were grouped according to mean preprandial glucose, we found that mean postprandial glucose increased across groups. However, IGP after a meal negatively correlated with preprandial glucose levels, with r values in the range of 0.20–0.40 (Table 1Go). All these negative correlations were significant (P = 0.01). There was a strong correlation between IGP and absolute glucose peak (r = 0.81; P < 0.001). In the whole sample, both fasting (r = 0.35; P = 0.01) and 2-h (r = 0.38; P = 0.01) glucose levels, and absolute glucose peak (r = 0.41; P < 0.001) were significantly correlated to HbA1c.

Timing and reproducibility of IGP

Figure 2Go shows the home blood glucose profiles obtained on 3 different days. Blood glucose increase after meal was not different between days, with a high reproducibility for all values, including glucose peaks. The P values for the ANOVA for repeated measures were all above 0.1 (not significant). Moreover, IGP tended to occur at the same time. Ninety-five percent of the entire diabetic population studied (611 patients) had IGP occurring within 1 h from the start of the meal (257 at 30 min and 354 at 60 min).


Figure 2
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  		FIG. 2. Incremental glucose values after meal recorded at home on 3 different days in 644 diabetic patients. SD values are: 30 min (45, 48, and 44 mg/dl on d 1, 2, and 3, respectively); 60 min (47, 51, and 49 mg/dl); 90 min (26, 24, and 24 mg/dl); and 120 min (18, 19, and 20 mg/dl).

 
Relationship between IGP and therapy for diabetes

Patients were classified into two groups according to whether they received drug treatment (n = 343) or diet alone (m = 301). Patients on drug treatment were more likely to have greater IGP levels as also indicated by a progressive shift of patient’s number from quintiles 1–5: quintile 1, 114 patients on diet and 15 patients on drugs; and quintile 5, zero patients on diet and 128 patients on drug (P = 0.01). However, the timing of IGP was not different between the two groups (diet of drug), occurring for the most (94 and 95%, respectively) within 60 min after starting the meal.


   Discussion
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Discussion
References
 
The results of the present study show that in patients with type 2 diabetes, IGP was correlated with CIMT more than markers of chronic hyperglycemia, including HbA1c and fasting glucose concentration, as well as markers currently used to define postprandial hyperglycemia, such as 2-h blood glucose concentration. Moreover, post-meal glucose peak is reproducible in the same patient, and occurs within 1 h after start of meal. Together, these findings suggest that IGP describes at best the cardiovascular risk associated with acute glucose swings and occurs commonly in the everyday life of the diabetic patient. The vast majority of patients (94%) recorded blood glucose exceeding the American Diabetes Association and World Health Organization and thresholds for unacceptable postprandial hyperglycemia (≥160 mg/dl, 8.89 mmol/liter) (25) at any time after the meal. About 33% of patients studied had IGP decreasing in the range of 0–50 mg/dl; this may be due to an awareness of being in the study, influencing actual carbohydrate intake, or additional variables such as concomitant medications other than those asked for.

A stronger correlation between post-challenge hyperglycemic spikes compared with 2-h post-challenge hyperglycemia and CIMT has already been reported (26); however, to our knowledge, this is the first demonstration that IGP assessed at home in a free living condition is the best predictor of CIMT among all glycemic parameters usually used to identify hyperglycemia, both chronic and postprandial hyperglycemia (19, 26). Other risk factors of atherosclerosis such as hypertension, regular smoking, hyperlipidemia, and obesity (22, 27, 28) have also been described as being associated with CIMT. However, we found no correlation between CIMT and such parameters as BMI, blood pressure, and serum lipid concentrations.

The metabolic abnormalities that characterize the development of type 2 diabetes are first demonstrated before clinical diabetes by elevations in postprandial glucose, due to the loss of first-phase insulin secretion, decreased insulin sensitivity in peripheral tissues, and reduced suppression of hepatic glucose output after meals due to insulin deficiency (29, 30). Monnier et al. (31) demonstrated that the gradual loss in daytime postprandial glycemic control precedes a stepwise deterioration in nocturnal fasting periods with worsening diabetes. In particular, nocturnal fasting glycemic control remains essentially unchanged as long as the HbA1c level is less than 8%, whereas postprandial glucose control is subject to much earlier deterioration, occurring as soon as HbA1c levels increase above 6.5%. Thus, a patient who had relatively normal fasting glucose values will exhibit abnormal elevations of glucose levels after meals. These findings are supported by interventional trials showing that patients who achieved fasting plasma glucose below the targets still exhibited A1C levels more than 7% (32).

Post-meal glucose levels seldom increase above 140 mg/dl (7.77 mmol/liter) in subjects with normal glucose tolerance and then return to basal levels 2–3 h after food ingestion (33, 34). However, the current consensus of the American Diabetes Association is that postprandial glucose should not necessarily be systematically monitored, and that postprandial glucose peaks should not necessarily be targeted and corrected (34), although, if monitored, the recommended goal for postprandial glucose is less than 10.0 mmol/liter (180 mg/dl) (35). Bonora et al. (19) obtained daily glucose profiles from 3284 type 2 diabetic patients and recorded a postprandial glucose value more than 160 mg/dl (8.89 mmol/liter) at least once in 84% of patients. These figures are consistent with data on post-oral glucose tolerance test hyperglycemia collected in diabetic patients from the National Health and Nutrition Examination Survey (18).

Large epidemiological studies have shown a strong association between post-meal and post-challenge glycemia and cardiovascular risk and outcomes in individuals with normal glucose tolerance, impaired glucose tolerance, or diabetes (9, 10, 36, 37). Furthermore, a large and growing body of evidence shows a causal relationship between post-meal hyperglycemia and oxidative stress, carotid atherosclerosis and endothelial dysfunction, all of which are known markers of cardiovascular disease (12, 13, 14, 15, 38, 39). Monnier et al. (40) assessed 24-h urinary excretion rates of free 8-iso prostaglandin F2{alpha} as a reliable marker of oxidative stress and used continuous glucose monitoring to assess glucose fluctuations. Results showed that glucose fluctuations during postprandial periods exhibited a more specific triggering effect on oxidative stress than chronic sustained hyperglycemia in type 2 diabetic patients compared with nondiabetic subjects.

Interventional trials also suggest a link between postprandial hyperglycemia and cardiovascular risk. The Study to Prevent Non-Insulin-Dependent Diabetes Mellitus trial has shown that treatment of subjects with impaired glucose tolerance with the {alpha}-glucosidase inhibitor acarbose, a compound that specifically reduces postprandial hyperglycemia, is associated with a 36% reduction in the risk of progression to diabetes (41), 34% risk reduction in the development of new cases of hypertension, 49% reduction in the risk of cardiovascular events (42), and a slower progression of CIMT (43). We have previously reported (23) a significant positive effect of post-meal glucose control on CIMT in 175 drug naive type 2 diabetic patients who were treated with repaglinide, a rapid-acting secretagogue that targets post-meal glucose. After 12 months, CIMT regression, defined as a decrease of more than 0.020 mm, was observed in 52% of diabetics receiving repaglinide and in 18% of those receiving glyburide.

In conclusion, this study demonstrates that an IGP value higher than 50 mg/dl (2.78 mmol/liter) is a frequent event in the everyday life of type 2 diabetes, occurs in about two thirds of patients, and correlates with CIMT. Moreover, 2-h postprandial glucose should not be considered as equivalent to post-meal glucose peak. For practical purposes, a 1-h glucose reading after meal represents a good estimate of absolute glucose peak (r = 0.84; P < 0.001), but future research on this topic is needed. Weaknesses of the present study are its observational nature, and results limited to people with type 2 diabetes and poor glycemic control. Strengths of the study are home assessment of glucose values instead of the artificial context of an oral glucose tolerance test, repetition of glucose profile within 1 month, centralization of analyses and CIMT, and the quite large number of patients investigated. Attention to post-meal glucose peak hopefully will provide an additional benefit to efforts to normalize HbA1c and premeal glucose value.


   Acknowledgments
 
The Campanian Post-Prandial Hyperglycemia Study Group: Carmen Di Palo, M.D., Domenico Di Tommaso, M.D., Donato Di Tommaso, M.D., Gennaro D’Orta, Technician, Giovanni Feola, M.D., Roberto Gualdiero, M.D., Maria Rosaria Improta, M.D., Alessandro Pontillo, M.D., Marilena Rispoli, M.D., and Luigi Sardelli, M.D., Division of Metabolic Diseases, Second University of Naples, Naples, Italy; Emilio Bellinfante, M.D., Simona Iuliano, M.D., Emilia Maglione, M.D., Lucio Misso, M.D., Franco Saccomanno, M.D., and Antonietta Santorelli, M.D., Diabetes Clinic, Second University of Naples, Naples, Italy; Sandro Gentile, M.D., and Ferdinando Sasso, M.D., Division of Internal Medicine, Second University of Naples, Naples, Italy; Riccardo Autorino, M.D., and Francesco Giugliano, M.D., Division of Urology, Second University of Naples, Naples, Italy; Flora Beneduce, M.D., ASLNA5, Italy; Renato Carleo, M.D., San Gennaro Hospital, Naples, Italy; Franco Carlino, M.D., AID Diabetes Clinic, Caserta, Italy; Antonio De Matteo, M.D., ASLNA1 (District 44), Naples, Italy; Paola Mattei, M.D., ASLNA1 (District 53), Naples, Italy; Elisa Migliaro, M.D., ASLNA1 (District 48), Naples, Italy; Sabato Mignano, M.D., ASLNA1 (District 52), Naples, Italy; Antonio Salomone, M.D., ASLNA3, Frattamaggiore, Italy; Michele Cutolo, M.D., ASLNA4, San Giuseppe Vesuviano, Italy; and Luciano Improta, M.D., ASLNA5, Italy.


   Footnotes
 
Disclosure Statement: The authors have nothing to declare.

First Published Online January 15, 2008

Abbreviations: BMI, Body mass index; CIMT, carotid intima-media thickness; HbA1c, glycosylated hemoglobin; HDL, high-density lipoprotein; IGP, incremental glucose peak.

Received September 6, 2007.

Accepted January 4, 2008.


   References
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Discussion
 References
 

  1. International Diabetes Federation 2006 Available from www.idf.org
  2. 1993 The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med 329:977–986
  3. 1995 The relationship of glycemic exposure (HbA1c) to the risk of development and progression of retinopathy in the diabetes control and complications trial. Diabetes 44:968–983
  4. Ohkubo Y, Kishikawa H, Araki E, Miyata T, Isami S, Motoyoshi S, Kojima Y, Furuyoshi N, Shichiri M 1995 Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study. Diabetes Res Clin Pract 28:103–117[CrossRef][Medline]
  5. 1998 Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet [Erratum (1999) 354:602] 352:837–853
  6. Stettler C, Allemann S, Juni P, Cull CA, Holman RR, Egger M, Krahenbhul S, Diem P 2006 Glycemic control and macrovascular disease in types 1 and 2 diabetes mellitus: meta-analysis of randomized trials. Am Heart J 152:27–38[CrossRef][Medline]
  7. Nathan DM, Buse JB, Davidson MB, Heine RJ, Holman RR, Sherwin R, Zinman B 2006 Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 29:1963–1972[Free Full Text]
  8. Sorkin JD, Muller DC, Fleg JL, Andres R 2005 The relation of fasting and 2-h postchallenge plasma glucose concentrations to mortality: data from the Baltimore Longitudinal Study of Aging with a critical review of the literature. Diabetes Care 28:2626–2632[Abstract/Free Full Text]
  9. Shiraiwa T, Kaneto H, Miyatsuka T, Kato K, Yamamoto K, Kawashima A, Kanda T, Suzuki M, Imano E, Matsuhisa M, Hori M, Yamasaki Y 2005 Postprandial hyperglycemia is a better predictor of the progression of diabetic retinopathy than HbA1c in Japanese type 2 diabetic patients. Diabetes Care 28:2806–2807[Free Full Text]
  10. Levitan EB, Song Y, Ford ES, Liu S 2004 Is nondiabetic hyperglycemia a risk factor for cardiovascular disease? A meta-analysis of prospective studies. Arch Intern Med 164:2147–2155[Abstract/Free Full Text]
  11. Hanefeld M, Cagatay M, Petrowitsch T, Neuser D, Petzinna D, Rupp M 2004 Acarbose reduces the risk for myocardial infarction in type 2 diabetic patients: meta-analysis of seven long-term studies. Eur Heart J 25:10–16[Abstract/Free Full Text]
  12. Giugliano D, Marfella R, Coppola L, Verrazzo G, Acampora R, Giunta R, Nappo F, Lucarelli C, D’Onofrio F 1997 Vascular effects of acute hyperglycemia in humans are reversed by L-arginine. Evidence for reduced availability of nitric oxide during hyperglycemia. Circulation 95:1783–1790[Abstract/Free Full Text]
  13. Williams SB, Goldfine AB, Timimi FK, Ting HH, Roddy MA, Simonson DC, Creager MA 1998 Acute hyperglycemia attenuates endothelium-dependent vasodilation in humans in vivo. Circulation 97:1695–1701[Abstract/Free Full Text]
  14. Marfella R, Quagliaro L, Nappo F, Ceriello A, Giugliano D 2001 Acute hyperglycemia induces an oxidative stress in healthy subjects. J Clin Invest 108:635–636[CrossRef][Medline]
  15. Scognamiglio R, Negut C, De Kreutzenberg SV, Tiengo A, Avogaro A 2005 Postprandial myocardial perfusion in healthy subjects and in type 2 diabetic patients. Circulation 112:179–184[Abstract/Free Full Text]
  16. 1996 The absence of a glycemic threshold for the development of long-term complications: the perspective of the Diabetes Control and Complications Trial. Diabetes 45:1289–1298
  17. Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, Hadden D, Turner RC, Holman RR 2000 Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ 321:405–412[Abstract/Free Full Text]
  18. Erlinger TP, Brancati FL 2001 Postchallenge hyperglycemia in a national sample of U.S. adults with type 2 diabetes. Diabetes Care [Erratum (2002) 25:249] 24:1734–1738[CrossRef]
  19. Bonora E, Corrao G, Bagnardi V, Ceriello A, Comaschi M, Montanari P, Meigs JB 2006 Prevalence and correlates of post-prandial hyperglycaemia in a large sample of patients with type 2 diabetes mellitus. Diabetologia 49:846–854[CrossRef][Medline]
  20. 2007 AACE Diabetes Mellitus Clinical Practice Guidelines Task Force, American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice of the Management of Diabetes Mellitus. Endocr Pract 13(Suppl 1):5-68
  21. 2006 Global guideline for type 2 diabetes. International Diabetes Federation Task Force on Clinical Guidelines, International Diabetes Federation. http://www.idf.org
  22. O’Leary LH, Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson Jr SK 1999 Carotid-artery intima and media thickness as a risk factor for myocardial infarction and stroke in older adults. Cardiovascular Health Study Collaborative Research Group. N Engl J Med 340:14–22[Abstract/Free Full Text]
  23. Esposito K, Giugliano D, Nappo F, Marfella R 2004 Regression of carotid atherosclerosis by control of postprandial hyperglycemia in type 2 diabetes mellitus. Circulation 110:214–219[Abstract/Free Full Text]
  24. Zar JH 1999 Biostatistical analysis. 4th ed. Upper Saddle River, NJ: Prentice Hall Inc.; 663
  25. 1999 A desktop guide to type 2 diabetes mellitus. European Diabetes Policy Group 1999. Diabet Med 16:716–730
  26. Temelkova-Kurktschiev TS, Koehler C, Henkel E, Leonhardt W, Hanefeld M 2000 Postchallenge plasma glucose and glycemic spikes are more strongly associated with atherosclerosis than fasting glucose or HbA1c levels. Diabetes Care 23:1830–1834[Abstract/Free Full Text]
  27. Burke GL, Evans GW, Riley WA, Sharrett AR, Howard G, Barnes RW, Rosamond W, Crow RS, Rautaharju PM, Heiss G 1995 Arterial wall thickness is associated with prevalent cardiovascular disease in middle-aged adults: the Atherosclerosis Risk in Communities (ARIC) Study. Stroke 26:386–391[Abstract/Free Full Text]
  28. Azen SP, Mack WJ, Cashin-Hemphill L, LaBree L, Shircore AM, Selzer RH, Blankenhom DH, Hodis HN 1996 Progression of coronary artery disease predicts clinical coronary events: long-term follow-up from the Cholesterol Lowering Atherosclerosis Study. Circulation 93:34–41[Abstract/Free Full Text]
  29. Weyer C, Bogardus C, Mott DM, Pratley RE 1999 The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus. J Clin Invest 104:787–794[Medline]
  30. Pratley RE, Weyer C 2001 The role of impaired early insulin secretion in the pathogenesis of type II diabetes mellitus. Diabetologia 44:929–945[CrossRef][Medline]
  31. Monnier L, Collette C, Dunseath GJ, Owens DR 2007 The loss of postprandial glycemic control precedes stepwise deterioration of fasting with worsening diabetes. Diabetes Care 30:263–269[Abstract/Free Full Text]
  32. Yki-Jarvinen H, Kauppinen-Makelin R, Tiikkainen M, Vähätalo M, Virtamo H, Nikkilä K, Tulokas T, Hulme S, Hardy K, McNulty S, Hänninen J, Levänen H, Lahdenperä S, Lehtonen R, Ryysy L 2006 Insulin glargine or NPH combined with metformin in type 2 diabetes: the LANMET study. Diabetologia 49:442–451[CrossRef][Medline]
  33. Polonsky KS, Given BD, Van Cauter E 1988 Twenty-four-hour profiles and pulsatile patterns of insulin secretion in normal and obese subjects. J Clin Invest 81:442–448[Medline]
  34. American Diabetes Association 2001 Postprandial blood glucose. American Diabetes Association. Diabetes Care 24:775–778[Free Full Text]
  35. American Diabetes Association 2005 Standards of medical care in diabetes. Diabetes Care [Erratum (2005) 28:990] 28(Suppl 1):S4–S36
  36. Gerich JE 2003 Clinical significance, pathogenesis, and management of postprandial hyperglycemia. Arch Intern Med 163:1306–1316[Abstract/Free Full Text]
  37. Cavalot F, Petrelli A, Traversa M, Bonomo K, Fiora E, Conti M, Anfossi G, Costa G, Trovati M 2006 Postprandial blood glucose is a stronger predictor of cardiovascular events than fasting blood glucose in type 2 diabetes mellitus, particularly in women: lessons from the San Luigi Gonzaga Diabetes Study. J Clin Endocrinol Metab 91:813–819[Abstract/Free Full Text]
  38. Kawano H, Motoyama T, Hirashima O, Hirai N, Miyao Y, Sakamoto T, Kugiyama K, Ogawa H, Yasue H 1999 Hyperglycemia rapidly suppresses flow-mediated endothelium-dependent vasodilation of brachial artery. J Am Coll Cardiol 34:146–154[Abstract/Free Full Text]
  39. Ceriello A, Quagliaro L, Piconi L, Assaloni R, Da Ros R, Maier A, Esposito K, Giugliano D 2004 Effect of postprandial hypertriglyceridemia and hyperglycemia on circulating adhesion molecules and oxidative stress generation and the possible role of simvastatin treatment. Diabetes 53:701–710[Abstract/Free Full Text]
  40. Monnier L, Mas E, Ginet C, Michel F, Villon L, Cristol JP, Colette C 2006 Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA 295:1681–1687[Abstract/Free Full Text]
  41. Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M, STOP-NIDDM Trial Research Group 2002 Acarbose for prevention of type 2 diabetes mellitus: the STOP-NIDDM randomised trial. Lancet 359:2072–2077[CrossRef][Medline]
  42. Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M, STOP-NIDDM Trial Research Group 2004 Acarbose for the prevention of type 2 diabetes, hypertension and cardiovascular disease in subjects with impaired glucose tolerance: facts and interpretations concerning the critical analysis of the STOP-NIDDM Trial data. Diabetologia 47:969–975[Medline]
  43. Hanefeld M, Chiasson JL, Koehler C, Henkel E, Schaper F, Temelkova-Kurktschiev T 2004 Acarbose slows progression of intima-media thickness of the carotid arteries in subjects with impaired glucose tolerance. Stroke 355:1073–1078



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